Metabolism of Leucine in Regulation of Insulin Secretion from Pancreatic Beta Cells (A Study in Khartoum State)

Branched-chain amino acids (BCAAs), including leucine, isoleucine and valine, are essential amino acids that cannot be manufactured in humans or other vertebrates and thus must be supplied in daily diet. BCAAs, in particular leucine, play a critical role in controlling protein synthesis by modulating translation initiation in various cells. Leucine is well known to acutely stimulate insulin secretion from pancreatic cells by serving as both metabolic fuel and allosteric activator of glutamate dehydrogenase (GDH) (1) (2) (3). Recent reports indicate that leucine or its transaminated product -ketoisocaproate (KIC) might impact on insulin secretion via a direct inhibition of cell KATP currents (4). In the past decade, leucine had been demonstrated to activate the mammalian target of rapamycin (mTOR), a serine and threonine protein kinase that regulates protein synthesis and cell metabolism, in pancreatic cells (5). To date, leucine has been proven to stimulate gene transcription and protein synthesis in pancreatic islets or other cell types by both mTOR-dependent and -independent pathways (6) (7) (8) (9). Leucine was reported to affect glucagon and insulin secretion in the pancreas (10) To our knowledge no research have been done to investigate leucine amino acid associated with insulin secretion in diabetic patients type two in Sudan. In this study, we intended to to find differences in the levels of leucine between Sudanese patients with diabetes mellitus type 2. and a control group. . and to measure the serum level of insulin in Sudanese patients with diabetes mellitus type 2. To correlate between the serum levels of leucine and the serum levels of insulin in Sudanese patients with diabetes mellitus type 2. To assess the relationship between the serum levels of leucine and the serum levels of insulin versus HbA1c, Body mass index, duration of diabetes. To determine age, gender, life style association with diabetes mellitus type 2 in Sudan. Method Descriptive analytic cross sectional and hospital based study. Samples were collected from different diabetes centers and hospitals in Khartoum state, Serum levels of leucine were measured using amino acid auto analyzer. Serum levels of insulin hormone were measured using ELIZA technique. HbA1c percentage were measured by ion exchange resin chromatography. Result 87 Sudanese patients with type2 diabetes mellitus were enrolled in this study in contrast to 10 healthy volunteers (Age and sex matched) as control.53 male, 44 female. the age range from 20 to 80, our results showed significantly higher levels of leucine among the diabetic patients (mean=494.390) compared to a control group (mean=330.007), also significantly higher levels of insulin was observed among the diabetic patients (mean=15.912) compared to a control group (mean=7.72), our results showed significantly higher levels of HA1C (mean=8.9) in diabetic patients compared to a control group (mean=5.3) conclusion and recommendation Significant difference in levels of insulin between diabetics and non-diabetics were observed. The altered levels of insulin in diabetic patients could be a suitable predictor of increasing leucine in their blood sample, is a condition in which there are excess levels of leucine circulating in the blood