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Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil and * Departamento de Fisiologia Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brazil
2To whom correspondence should be addressed. E-mail: boschero{at}unicamp.br.
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • protein restriction • gene expression • cDNA array • pancreatic islets
Adequate nutrition during the prenatal and early postnatal periods is very important for the development of the endocrine pancreas. Epidemiologic data from different human and animal studies showed that poor nutrition during these periods of life is associated with an increased incidence of glucose intolerance and type 2 diabetes in adulthood (1).
Several studies have associated the control of gene expression with nutritional signals (2–6). The availability of free amino acids in the diet is important for maintaining protein homeostasis, and a deficiency in any of the essential amino acids can lead to a negative nitrogen balance. Alterations in nitrogen metabolism change the plasma amino acid profile (7–11). As a consequence, gene expression and physiologic functions are altered to cope with the limited availability of amino acids (12–14).
Intrauterine malnutrition induced by feeding dams a low protein diet during pregnancy and lactation also affects the structure and function of several organs in the offspring. A reduction in insulin secretion in response to glucose and different secretagogues, a reduction in the rate of islet-cell proliferation, and a reduction in islet size and vascularization were observed in the endocrine pancreas of malnourished rats (15–18). Alterations in the plasma amino acid profiles of dams and offspring occur when a low protein diet is introduced during gestation.
In this study, we examined the influence of dietary protein restriction on islet gene expression. Pancreatic islet RNA from rats fed low and normal protein diets was reverse-transcribed and hybridized to the Atlas cDNA array (Clontech), a commercial nylon membrane containing 1176 genes. The results of the macroarray analysis were confirmed by RT-PCR for five selected genes.
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MATERIALS AND METHODS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Amino acid profile. Plasma samples were collected from fed and food-deprived (13 h) rats (NP and LP groups). The samples were deproteinized by adding 1 mL of 25% trichloroacetic acid (TCA) solution to 1 mL of plasma followed by storage at 4°C for 1 h. After centrifugation at 10,000 x g, 30 µL of the supernatant was mixed with 60 µL loading sample buffer (Biochrom 20 reagent kit), and 20 µL was analyzed by chromatography on a Biochrom 20 plus (Amersham Pharmacia, Piscataway, NJ) using a specific physiologic amino acid column. FFA standards were analyzed first, followed by the samples. Amino acids were quantified using Biochrom 20 control software version 3.05. Ammonia was also measured as an internal control for estimation of amino acid degradation.
Pancreatic islet isolation and static insulin secretion. Wistar rats were decapitated and the islets were isolated by handpicking under a stereomicroscope after collagenase digestion of the pancreas, as previously described (24). Groups of five islets were first incubated for 45 min at 37°C in Krebs-bicarbonate buffer with the following composition (mmol/L): NaCl, 115; KCl, 5; CaCl2, 2.56; MgCl2, 1; NaHCO3, 24 and glucose, 5.6, supplemented with 3 g of bovine serum albumin/L and equilibrated with a mixture of 95% O2/5% CO2, pH 7.4. This medium was then replaced with fresh buffer and the islets were incubated with glucose (5.6; 8.3 or 16.7 mmol/L) for 1 h. The insulin in the medium at the end of the incubation period was measured by RIA (23).
Macroarray analysis.
RNA was isolated from islets using the TRIzol reagent/phenol/chloroform procedure (Life Technologies, Auckland, New Zealand), followed by digestion of genomic DNA with RNase-free DNase. The quality and purity of the RNA were analyzed by electrophoresis in denaturing gels and PCR. Radiolabeled cDNA was prepared using 5 µg of total RNA in 10 µL of 50 mmol/L Tris-HCl (pH 8.3) containing 75 mmol/L KCl, 3 mmol/L MgCl2, 0.5 mmol/L of a dNTP mixture without dATP, 5 mmol/L dithiothreitol, gene-specific CDS primer mix (a mix of primers specific for each type of atlas array) (Clontech), and Maloney murine leukemia virus reverse transcriptase (Clontech) in the presence of 35 µCi [
-33P] dATP (3000 Ci/mmol; Amersham). After incubation at 50°C for 25 min, the reaction was stopped by adding 0.01 mol/L EDTA (pH 8.0). The cDNA generated was purified by column chromatography (Chroma Spin-200 DEPC-H2O columns, Clontech).
The arrays were performed, in parallel, under identical conditions according to the manufacturer’s instructions (Clontech). The Atlas rat array 1.2 consisted of 1176 genes spotted on positively charged nylon membranes. Plasmid and bacteriophage DNAs were included as negative controls to confirm hybridization specificity, and housekeeping cDNAs were used as positive controls to normalize the mRNA abundance. All of the cDNAs and controls immobilized on the membrane were grouped into several clusters according to their functions (25).
The membranes were prehybridized in ExpressHyb buffer containing 0.5 mg of heat denatured sheared salmon DNA at 68°C for 30 min. Labeled cDNA probe was added to the prehybridization buffer (30–170 kBq/membrane) and hybridization was continued overnight at 68°C. The membranes were washed and exposed directly to a storage phosphor screen (Molecular Dynamics). The screens were scanned using Storm 840. Signal intensities captured from each spot by Array Vision Evaluation 7.0 software were normalized using the intensities of the housekeeping genes [polyubiquitin, phospholipase A2 group IB (PLA2G1B) and ribosomal protein S29] provided in the array. This normalization allowed a quantitative comparison of the signal intensity of each gene on membranes from rats fed LP and NP. Differentially expressed genes were identified using Microsoft Excel XP. The result for each gene was expressed as the fold change in rats fed LP relative to the NP controls (expression arbitrarily designated as 1). The differences in gene expression in rats fed LP were considered relevant when the fold change was 
2.0 (up-regulated) or 
0.5 (down-regulated) compared with rats fed NP. The experiment was done twice using cDNA obtained from two different sets of 5 rats and new membranes each time. The genes were classified into different functional clusters on the basis of the putative biological function of the encoded protein, as determined by relevant database searches (26).
RNA isolation and RT-PCR. Semiquantitative RT-PCR was done to validate the findings of gene transcript expression shown by macroarray analysis. Briefly, total RNA was extracted from 300 islets obtained from rats fed LP and NP using the TRIzol reagent/phenol/chloroform procedure (Invitrogen). Before RT, the quality, purity and lack of contamination by genomic DNA were assessed by electrophoresis in denaturing gels, DNase treatment and PCR, respectively. Reverse transcription was done with 2 µg of total RNA using Moloney murine leukemia virus-reverse transcriptase (SuperScript II) and random hexamers, according to the manufacturer’s instructions (Invitrogen). The cDNA obtained was stored at -20°C.
The PCR were then done in a 25-µL reaction volume containing 1 µL cDNA, 0.05 mmol/L of each cold dNTP (dATP, dCTP, dTTP, dGTP), 0.37 mmol/L MgCl2, 0.25X PCR buffer, 0.1 µmol/L of appropriate oligonucleotide primers (Table 1) and 1 U of Taq DNA polymerase (Invitrogen). The number of cycles was selected to allow linear amplification of the cDNA.
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The amplified products were analyzed by electrophoresis in 1.8% agarose gels in Tris-borate-EDTA buffer 1X and stained with ethidium bromide. All reactions included a negative control. Subsequent digitalization and relative band intensities were done using an Eagle Eye II documentation system (Stratagene, La Jolla, CA). The results were expressed as a ratio of the target to standard signals.
Statistical analysis. The results are expressed as means ± SEM. Student’s unpaired t test was generally used to compare NP and LP groups. Insulin secretion data were log-transformed to correct for heterogeneity in variance and then analyzed by two-way ANOVA, followed by the Tukey-Kramer test to determine the significance of differences between groups and among glucose and secretagogue concentrations, and to assess the interactions between these factors. The data were analyzed using the Statistica software package (Statsoft, Tulsa, OK) and the level of significance was set at P < 0.05.
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RESULTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Amino acids profile. Plasma amino acid concentrations in rats fed LP differed from those in the NP rats under both fed and food-deprived conditions (Table 2). Food-deprived LP rats had decreased levels of several amino acids, including taurine, aspartate, glutamate, glutamine, proline, methionine, ß-alanine, phenylalanine, homocysteine, ornithine, histidine and increased levels of asparagine, serine, sarcosine, glycine, alanine, leucine, tyrosine, lysine and arginine compared with food-deprived NP rats. In contrast, in the fed state, LP rats had decreased levels of taurine, threonine, asparagine, glutamate, proline, valine, methionine, isoleucine, phenylalanine, hydroxylysine and arginine, whereas the levels of serine, glutamine, sarcosine, glycine, alanine, leucine, lysine and ß-alanine were increased compared with rats fed NP.
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subunit (EIF2-), secretogranin precursor, glucose transporter-2 (GLUT2), clusterin and PLA2G1B. RT-PCR confirmed the macroarray results for all of these genes. The EIF2- and PLA2G1B mRNA concentrations did not differ in islets from NP and LP rats (Fig. 2A, E). In contrast, the mRNA concentrations for secretogranin (32%), GLUT-2 (53%) and clusterin (31%) were significantly lower in islets from LP rats (P < 0.05) (Fig. 2B, 2D). The expression of PVX did not differ in islets from LP and NP rats when analyzed by RT-PCR (Fig. 2F). This result validates the use of this external standard/control for normalizing the gene expression in RT-PCR.
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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As expected, LP rats showed features typical of malnutrition, including low body weight, low levels of serum albumin and insulin, and higher liver glycogen and fat contents. Despite a significant reduction in insulinemia, glycemia was unaltered in rats fed LP compared with rats fed NP. These findings may be related to a marked increase in insulin sensitivity through an increase in the phosphorylation of the insulin receptor and insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase (18,19,35).
Levels of valine, isoleucine, methionine, phenylalanine and threonine were lower in LP-fed rats. These amino acids are considered essential and a deficiency in any of them could lead to a negative nitrogen balance with clinical consequences (13). In addition, the amino acid taurine was reduced in both fed and food-deprived LP rats. Taurine influences glucose metabolism and consequently increases insulin secretion. A deficiency in taurine slows growth, decreases insulin secretion and induces cardiac dysfunction and immunological insufficiency (37–39).
Leucine, a stimulator of insulin secretion was also diminished in rats fed LP. The metabolization of leucine via the Krebs’ cycle or by mitochondrial oxidation in ß-cells can elevate the ATP/ADP ratio; this in turn may stimulate the release of insulin (40,41). Previous work showed that leucine-induced insulin secretion is affected by a low protein diet (18).
To assess the possible global transcriptional modifications caused by a low protein diet, a cDNA macroarray was used to monitor and compare gene expressions. The Atlas cDNA array 1.2, which contains 1176 genes, was used in this study. In islets from rats fed LP, 32 genes showed an altered expression when compared with islets of NP-fed rats. Tables 3, and 4 show that there were metabolic and structural adaptations in pancreatic islets from rats fed LP.
The expression of the GLUT-2 gene and its respective protein (measured by Western blotting, not shown) was reduced in islets from rats fed LP. Using knockout mice for GLUT-2, Thorens et al. (42) showed a total loss of the first phase of glucose-stimulated insulin secretion and a reduced second phase during perfusion experiments. A similar pattern of insulin secretion was observed for islets from pups of dams fed a low protein diet during pregnancy and lactation (35). These results are consistent with GLUT-2 acting as a glucose sensor and regulator of glucose metabolism.
Islets from rats fed LP showed increased expression of muscle phosphofructokinase (PFK), a tetrameric protein with three isoforms, designated M (muscle), P (platelet) (or C) and L (liver), involved in the glycolytic pathway (43,44). All three isoforms were detected in pancreatic islets and clonal pancreatic ß-cells (INS-1) (44,45). The autocatalytic activation of PFK by its product, fructose 1,6-bisphosphate, generates glycolytic oscillations. The overexpression of PFK in transgenic mice results in defective glucose metabolism followed by impaired glucose-induced insulin secretion (46). Thus, alterations in the levels of PFK isoforms may lead to changes in the enzymes properties and activity, and this could decrease glucose-induced insulin secretion.
Voltage-gated ion channels play an important role in the insulin secretion stimulated by glucose and other insulinotropic agents. An increase in the ATP/ADP ratio through glucose metabolism closes KATP channels and depolarizes ß-cells. This depolarization leads to the opening of voltage-dependent Ca2+ channels and an influx of calcium that triggers insulin granule exocytosis (47,48). In islets from rats fed LP, there is a decreased movement of intracellular calcium and a reduced expression of protein kinase C (PKC) (18,33,47). As shown here, there is also a reduced gene expression of voltage-gated K+ channel proteins. This finding could explain in part the poor secretory response to glucose and other secretagogues in rats fed LP.
Alterations in the expression of the G-protein Rab 26 were observed. Although the functions of this protein are not completely understood, some Ras-related proteins have been implicated in intracellular vesicular trafficking along the biosynthetic and endocytic pathways, with functional links to SNARE complexes (49–51). Sequence comparisons between Rab 26 and other Ras proteins described in the literature revealed closest homology to Rab 8, Rab 3A, Rab 15 and SEC4 (52). To our knowledge, there is no information on the effects of Rab 26 on insulin secretion. However, other members of the Rab family, such as Rab 3A, Rab 3B and Rab 3D, negatively modulate Ca2+-triggered exocytosis in ß-cells (53,54). Thus, it is conceivable that the increase in Rab 26 expression may be related to the reduced insulin secretion by islets from rats fed LP. In contrast, a decrease in calcium/calmodulin-dependent protein kinase expression was observed. This protein kinase is related to Ca2+ modulation and induction of insulin secretion and is the major Rab 3A-associating protein in pancreatic ß-cells (55,56).
Rats fed LP also had a 3.3-fold increase in carboxypeptidase D, an important enzyme present in the trans-Golgi network. This enzyme is responsible for the production of the peptides and proteins that transit the secretory and endocytic pathways, including the cleavage of C-terminal residues from prohormones (57). Interestingly, there was a reduction in the expression of secretogranin III. This protein is involved in the production or release of peptide hormones from the storage vesicles of neuroendocrine cells involved in the biogenesis of secretory granules (58,59).
A reduction in insulin-like growth factor-I (IGF-I) and IGF-II mRNA was observed in ß-cells from neonatal rats of dams fed a low protein diet during pregnancy (31). These growth hormones are regulated by the nutritional supply of dietary energy and protein and are able to increase islet cell DNA synthesis and proliferation, thus providing an important link between nutrition and growth (31). In the present study, we observed an increase in IGF-II mRNA, suggesting an increase in proliferation rates.
Elevated levels of matrix metalloproteinase (MMP) 14 were also observed in our analysis. Matrix metalloproteinases are extracellular proteinases important for cell migration, invasion, proliferation and apoptosis; their main function is presumed to be remodeling of the extracellular matrix (60). In contrast to MMP-14, other genes related to cell growth, differentiation and cellular responses to infection/injury, such as STAT3 (61), were concomitantly diminished.
The decreased expression in LP of genes belonging to the intracellular kinase network, such as mitogen-activated protein kinase 2 (MAPK2) and insulin-stimulated microtube-associated protein kinase 2 (MAP2 kinase), suggested alterations in certain signal transduction pathways. Previous studies in INS-1 cells and rat islets indicated that MAP were not involved in insulin secretion (62), but may be related to other ß-cell functions, such as metabolism, transcription, cell cycle progression, cytoskeletal rearrangements, cell movement, apoptosis and differentiation (63). In addition, there was a decrease in the mRNA of extracellular signal-regulated kinase 1 and 2 (ERK1, ERK2), which are involved in the regulation of meiosis and mitosis in differentiated cells.
In rats fed a high-carbohydrate (HC) diet milk, there was an immediate onset of hyperinsulinemia and up-regulation of preproinsulin gene transcription. cDNA array analysis of pancreatic islets from these rats showed that the HC diet up-regulated genes involved in metabolic pathways, ion channels, signal transduction, the cell cycle, protein synthesis and apoptosis (64,65). Increased expression of genes related to insulin biosynthesis/secretion, such as insulin, PDX-1, ACC, Reg III, Isl-1, GLUT-2, IRS-1 and IRS-2, was also observed. In contrast, we observed a decreased expression of PDX-1 (34), PKC (33), and PKA, insulin, GLUT-2 and IRS-1, as well as glucose metabolism (data not shown). Together, these findings indicate that it is unlikely that the carbohydrate added to the LP diet to compensate for the lack of protein was responsible for the alterations observed in the cDNA array. However, we cannot dismiss the possibility that the expression of some genes was affected by the higher glucose intake of rats fed LP compared with those fed NP.
In conclusion, the results of this study showed that a low protein diet altered the expression of several genes that encode for proteins related to insulin biosynthesis, secretion and cellular remodeling in rat pancreatic islets (Fig. 3). This altered expression could explain the reduced insulin secretion by islets from rats fed LP after stimulation.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: EIF2-, eukaryotic translation initiation factor 2 subunit; ERK, extracellular signal-regulated kinase; FFA, free fatty acid; GLUT2, glucose transporter 2; HC, high carbohydrate; IGF-I, insulin-like growth factor-I; LP, low protein group; MAP2 kinase, microtube-associated protein kinase 2; MAPK2, mitogen-activated protein kinase 2; MMP, metalloproteinases; NP, normal protein group; PFK, phosphofructokinase; PKC, protein kinase C; PLA2G1B, phospholipase A2 group IB; PVX, potato virus X; TCA, trichloroacetic acid; TTBS, Tris-Tween 20 buffered saline.
Manuscript received 2 July 2003. Initial review completed 12 August 2003. Revision accepted 23 October 2003.
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LITERATURE CITED |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Fowden, A. L. & Hill, D. J. (2001) Intra-uterine programming of the endocrine pancreas. Br. Med. Bull. 60:123-142.
2. Vaulont, S. & Kahn, A. (1994) Transcriptional control of metabolic regulation genes by carbohydrates. FASEB J 8:28-35.[Abstract]
3. Towle, H. C. (1995) Metabolic regulation of gene transcription in mammals. J. Biol. Chem. 270:23235-23238.
4. Foufelle, F., Girard, J. & Ferre, P. (1998) Glucose regulation of gene expression. Curr. Opin. Clin. Nutr. Metab. Care 1:323-328.[Medline]
5. Pegorier, J. P. (1998) Regulation of gene expression by fatty acids. Curr. Opin. Clin. Nutr. Metab. Care 1:329-334.[Medline]
6. Srinivasan, M., Song, F., Aalinkeel, R. & Patel, M. L. (2001) Molecular adaptations in islets from neonatal rats reared artificially on a high carbohydrate milk formula. J. Nutr. Biochem. 12:575-584.[Medline]
7. Harper, A. E. & Rogers, Q. R. (1965) Amino acid imbalance. Proc. Nutr. Soc. 24:173-190.[Medline]
8. Richardson, L. R., Hale, F. & Ritchey, S. J. (1965) Effect of fasting and level of dietary protein on free amino acids in pig plasma. J. Anim. Sci. 24:368-379.
9. Peng, Y., Meliza, L. L., Vavich, M. G. & Kemmerer, A. R. (1975) Effects of amino acid imbalance and protein content of diets on food intake and preference of young, adult, and diabetic rats. J. Nutr. 105:1395-1404.
10. Reusens, B., Dahri, S., Snoeck, A., Bennis-Taleb, N., Remacle, C. & Hoet, J. J. (1995) Long term consequences of diabetes and its complications may have a fetal origin: experimental and epidemiological evidence. Cowett, R. M. eds. Diabetes 35:187-198 Nestlé Nutrition Workshop Series Raven Press, New York, NY. .
11. Cetin, I. (2001) Amino acid interconversions in the fetal-placental unit: the animal model and human studies in vivo. Pediatr. Res. 49:148-154.[Medline]
12. Kilberg, M. S., Hutson, R. G. & Laine, R. O. (1994) Amino acid-regulated gene expression in eukaryotic cells. FASEB J 8:13-19.[Abstract]
13. Jousse, C., Bruhat, A. & Fafournoux, P. (1999) Amino acid regulation of gene expression. Curr. Opin. Clin. Nutr. Metab. Care 2:297-301.[Medline]
14. Fafournoux, P., Bruhat, A. & Jousse, C. (2000) Amino acid regulation of gene expression. Biochem. J. 351:1-12.[Medline]
15. Snoeck, A., Remacle, C., Reusens, B. & Hoet, J. J. (1990) Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biol. Neonate 57:107-118.[Medline]
16. Dahri, S., Snoeck, A., Reusens-Billen, B., Remacle, C. & Hoet, J. J. (1991) Islet function in offspring of mothers on low-protein diet during gestation. Diabetes 40(suppl. 2):115-120.
17. Hoet, J. J., Dahri, S., Snoeck, A., Reusens-Billen, B. & Remacle, C. (1992) Importance of diets and their effect on fetal development: function and structure of the endocrine pancreas following protein deficiency during intrauterine life. Bull. Mem. Acad. R. Med. Belg. 147:174-181.[Medline]
18. Latorraca, M. Q., Carneiro, E. M., Mello, M. A. & Boschero, A. C. (1999) Reduced insulin secretion in response to nutrients in islets from malnourished young rats is associated with a diminished calcium uptake. J. Nutr. Biochem. 10:37-43.
19. Reis, M. A., Carneiro, E. M., Mello, M. A., Boschero, A. C., Saad, M. J. & Velloso, L. A. (1997) Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats. J. Nutr. 127:403-410.
20. Doumus, B. T., Watson, W. A. & Biggs, H. G. (1971) Albumin standards and measurements of serum albumin with bromocresol green. Clin. Chim. Acta 31:87-96.[Medline]
21. Heard, C. R., Frangi, S. M., Wright, P. M. & McCartney, P. R. (1997) Biochemical characteristics of different forms of protein-energy malnutrition: an experimental model using young rats. Br. J. Nutr. 37:1-21.
22. Weinkove, C., Weinkove, E. A. & Pimstone, B. L. (1976) Glucose tolerance and insulin release in malnourished rats. Clin. Sci. Mol. Med. 50:153-163.[Medline]
23. Scott, A. M., Atwater, I. & Rojas, E. (1981) A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans. Diabetologia 21:470-475.[Medline]
24. Bordin, S., Boschero, A. C., Carneiro, E. M. & Atwater, I. (1995) Ionic mechanisms involved in the regulation of insulin secretion by muscarinic agonists. J. Membr. Biol. 148:177-184.[Medline]
25. http://www.bdbiosciences.com/atlas/genelists/index.shtml/7854–1. [Accessed May 02, 2003.].
26. http://www.ncbi.nlm.nih.gov/PubMed. [Accessed June 30, 2003.].
27. http//www. ncbi. nlm. nih. gov/BLAST. [Accessed January 20, 2002.].
28. Eickhoff, B., Korn, B., Schick, M., Poustka, A. & van der Bosch, J. (1999) Normalization of array hybridization experiments in differential gene expression analysis. Nucleic Acids Res 27:e33.
29. Hales, C. N., Desai, M., Ozanne, S. E. & Crowther, N. J. (1996) Fishing in the stream of diabetes: from measuring insulin to the control of fetal organogenesis. Biochem. Soc. Trans. 24:341-350.[Medline]
30. Berney, D. M., Desai, M., Palmer, D. J., Greenwald, S., Brown, A., Hales, C. N. & Berry, C. L. (1997) The effects of maternal protein deprivation on the fetal rat pancreas: major structural changes and their recuperation. J. Pathol. 183:109-115.[Medline]
31. Petrik, J., Reusens, B., Arany, E., Remacle, C., Coelho, C., Hoet, J. J. & Hill, D. J. (1999) A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II. Endocrinology 140:4861-4873.
32. Cherif, H., Reusens, B., Dahri, S. & Remacle, C. (2001) A protein-restricted diet during pregnancy alters in vitro insulin secretion from islets of fetal Wistar rats. J. Nutr. 131:1555-1559.
33. Ferreira, F., Filiputti, E., Arantes, V. C., Stoppiglia, L. F., Araujo, E. P., Delghingaro-Augusto, V., Latorraca, M. Q., Toyama, M. H., Boschero, A. C. & Carneiro, E. M. (2003) Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase C expression. J. Nutr. 133:695-699.
34. Arantes, V. C., Teixeira, V. P., Reis, M. A., Latorraca, M. Q., Leite, A. R., Carneiro, E. M., Yamada, A. T. & Boschero, A. C. (2002) Expression of PDX-1 is reduced in pancreatic islets from pups of rat dams fed a low protein diet during gestation and lactation. J. Nutr. 132:2030-2035.
35. Latorraca, M. Q., Carneiro, E. M., Boschero, A. C. & Mello, M. A. (1998) Protein deficiency during pregnancy and lactation impairs glucose-induced insulin secretion but increases the sensitivity to insulin in weaned rats. Br. J. Nutr. 80:291-297.[Medline]
36. Rao, R. H. (1988) Diabetes in the undernourished: coincidence or consequence?. Endocr. Rev. 9:67-87.
37. Lake, N., Wright, E. D. & Lapp, W. S. (1992) Effects of taurine deficiency on immune function in mice. Adv. Exp. Med. Biol. 315:241-243.[Medline]
38. Eley, D. W., Lake, N. & ter Keurs, H. E. (1994) Taurine depletion and excitation-contraction coupling in rat myocardium. Circ. Res. 74:1210-1219.
39. Cherif, H., Reusens, B., Ahn, M. T., Hoet, J. J. & Remacle, C. (1998) Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet. J. Endocrinol. 159:341-348.[Abstract]
40. Gao, Z., Young, R. A., Li, G., Najafi, H., Buettger, C., Sukumvanich, S. S., Wong, R. K., Wolf, B. A. & Matschinsky, F. M. (2003) Distinguishing features of leucine and alpha-ketoisocaproate sensing in pancreatic beta-cells. Endocrinology 144:1949-1957.
41. Li, C., Najafi, H., Daikhin, Y., Nissim, I. B., Collins, H. W., Yudkoff, M., Matschinsky, F. M. & Stanley, C. A. (2003) Regulation of leucine-stimulated insulin secretion and glutamine metabolism in isolated rat islets. J. Biol. Chem. 278:2853-2858.
42. Thorens, B. (2003) A gene knockout approach in mice to identify glucose sensors controlling glucose homeostasis. Pflugers. Arch. 445:482-490.[Medline]
43. Dunaway, G. A. & Kasten, T. P. (1987) Nature of the subunits of the 6-phosphofructo-1-kinase isoenzymes from rat tissues. Biochem. J. 242:667-671.[Medline]
44. Yaney, G. C., Schultz, V., Cunningham, B. A., Dunaway, G. A., Corkey, B. E. & Tornheim, K. (1995) Phosphofructokinase isozymes in pancreatic islets and clonal beta-cells (INS-1). Diabetes 44:1285-1289.[Abstract]
45. Eto, K., Sakura, H., Yasuda, K., Hayakawa, T., Kawasaki, E., Moriuchi, R., Nagataki, S., Yazaki, Y. & Kadowaki, T. (1994) Cloning of a complete protein-coding sequence of human platelet-type phosphofructokinase isozyme from pancreatic islet. Biochem. Biophys. Res. Commun. 198:990-998.[Medline]
46. Knobler, H., Weiss, Y., Peled, M. & Groner, Y. (1997) Impaired glucose-induced insulin response in transgenic mice overexpressing the L-phosphofructokinase gene. Diabetes 46:1414-1418.[Abstract]
47. Carneiro, E. M., Mello, M. A., Gobatto, C. A. & Boschero, A. C. (1995) Low protein diet impairs glucose-induced insulin secretion from and 45Ca uptake by pancreatic rat islets. Nutr. Biochem. 6:314-318.
48. Miki, T., Nagashima, K. & Seino, S. (1999) The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells. J. Mol. Endocrinol. 22:113-123.[Abstract]
49. Sogaard, M., Tani, K., Ye, R. R., Geromanos, S., Tempst, P., Kirchhausen, T., Rothman, J. E. & Sollner, T. (1994) A rab protein is required for the assembly of SNARE complexes in the docking of transport vesicles. Cell 78:937-948.[Medline]
50. Johannes, L., Doussau, F., Clabecq, A., Henry, J. P., Darchen, F. & Poulain, B. (1996) Evidence for a functional link between Rab3 and the SNARE complex. J. Cell. Sci. 109:2875-2884.[Abstract]
51. Lupashin, V. V. & Waters, M. G. (1997) t-SNARE activation through transient interaction with a rab-like guanosine triphosphatase. Science (Washington, DC) 276:1255-1258.
52. Wagner, A. C., Strowski, M. Z., Goke, B. & Williams, J. A. (1995) Molecular cloning of a new member of the Rab protein family, Rab 26, from rat pancreas. Biochem. Biophys. Res. Commun. 207:950-956.[Medline]
53. Easom, R. A. (2000) Beta-granule transport and exocytosis. Semin. Cell. Dev. Biol. 11:253-266.[Medline]
54. Kajio, H., Olszewski, S., Rosner, P. J., Donelan, M. J., Geoghegan, K. F. & Rhodes, C. J. (2001) A low-affinity Ca2+-dependent association of calmodulin with the Rab3A effector domain inversely correlates with insulin exocytosis. Diabetes 50:2029-2039.
55. Jones, P. M. & Persaud, S. J. (1998) Ca2+-induced loss of Ca2+/calmodulin-dependent protein kinase II activity in pancreatic beta-cells. Am. J. Physiol. 274:E708-E715.
56. Coppola, T., Perret-Menoud, V., Luthi, S., Farnsworth, C. C., Glomset, J. A. & Regazzi, R. (1999) Disruption of Rab3-calmodulin interaction, but not other effector interactions, prevents Rab3 inhibition of exocytosis. EMBO J 18:5885-5891.[Medline]
57. Sidyelyeva, G. & Fricker, L. D. (2002) Characterization of Drosophila carboxypeptidase D. J. Biol. Chem. 277:49613-49620.
58. Rong, Y. P., Liu, F., Zeng, L. C., Ma, W. J., Wei, D. Z. & Han, Z. G. (2002) Cloning and characterization of a novel human secretory protein: secretogranin III. Sheng Wu Hua Hsueh Yu Sheng Wu Wu Li Hsueh Pao 34:411-417.
59. Taupenot, L., Harper, K. L. & O’Connor, D. T. (2003) Mechanisms of disease: the chromagranin family. N. Engl. J. Med. 348:1134-1149.
60. Vu, T. H. & Werb, Z. (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14:2123-2133.
61. Bromberg, J. & Darnell, J. E., Jr (2000) The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19:2468-2473.[Medline]
62. Jones, P. M. & Persaud, S. J. (1998) Protein kinases, protein phosphorylation, and the regulation of insulin secretion from pancreatic beta-cells. Endocr. Rev. 19:429-461.
63. Johnson, G. L. & Lapadat, R. (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science (Washington, DC) 298:1911-1912.
64. Song, F., Srinivasan, M., Aalinkeel, R. & Patel, M. S. (2001) Use of a cDNA array for the identification of genes induced in islets of suckling rats by a high-carbohydrate nutritional intervention. Diabetes 50:2053-2060.
65. Srinivasan, M., Aalinkeel, R., Song, F., Lee, B., Laychock, S. G. & Patel, M. S. (2000) Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula. Am. J. Physiol. 279:E1347-E1357.
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-amino butyric acid; IGF, insulin-like growth factor; STAT, signal transducers and activators of transcription; MAPK, mitogen-activated protein kinase; ERK, extracellular signal-regulated kinase.