title: Branched-chain amino acids supplementation protects streptozotocin-induced insulin secretion and the correlated mechanism.
abstract: Significant evidence demonstrates that oxidative stress can impair insulin secretion and contribute to the development of type 2 diabetes. Branched-chain amino acids (BCAAs) are reported to be positively related to insulin secretion. This study aimed to determine how oxidative stress affects the function of islets and whether BCAAs can ameliorate the oxidative stress, and accompanying c-jun N-terminal kinase (JNK), protein kinase D1 (PKD1), and pancreatic/duodenal homeobox-1 (PDX-1) changes induced by streptozotocin (STZ). Plasma glucose, plasma insulin, and JNK, PKD1 and PDX-1 mRNA and protein expression were measured in rats treated with STZ and BCAAs. The glucose level in STZ-induced diabetic rats was much higher than that in control animals, and the elevated plasma glucose level in diabetic rats could be significantly inhibited by BCAAs treatment. Consistent with the change in glucose levels, the levels of insulin were also affected by BCAAs treatment. The mRNA and protein expression of JNK, PDX-1, and PKD1 were significantly altered in diabetic rats compared with the control group (P<0.01) and treatment with a low dose of BCAA reversed these changes in those above markers significantly (P<0.01). The present study demonstrated that STZ-induced oxidative stress could reduce serum insulin levels and alter the JNK, PDX-1, and PKD1 expression. BCAAs restored the levels of serum insulin reversed changes in JNK, PDX-1, and PKD1 expression.
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zheng
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Jiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000178:diet therapy* / Q000235:genetics; D005215:Fasting; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D061251:Primary Cell Culture; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013311:Streptozocin; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D013311:Streptozocin; C089212:protein kinase D; D011493:Protein Kinase C; D048670:MAP Kinase Kinase 4
keywords: JNK; Streptozotocin; branched-chain amino acids; insulin secretion; pancreatic/duodenal homeobox-1; protein kinase D1