[A study on the mechanism of islet cell insulin resistance in high-fat-diet obese rats].
OBJECTIVE
To study the changes of insulin signal transduction in islet cells of high-fat-diet rats with peripheral insulin resistance (IR).


METHODS
Thirty male Wistar rats were randomly divided into 2 equal groups: high-fat-diet group and control group to be fed with high-fat food and normal food respectively. Twenty weeks after the rats were sacrificed. The contents of insulin and glucagon in homogenate of pancreas were detected during islet cell perifusion, and insulin receptor (IRc) and insulin receptor substrates (IRS-1 and IRS-2) were detected by immunohistochemistry.


RESULTS
(1) The insulin sensitive index (ISI) was significantly decreased in the high-fat-diet rats in comparison with the normal rats, while the contents of glucagon in blood and in homogenate of pancreas were both significantly increased in the high-fat-diet rats (362 pg/ml +/- 58 pg/ml vs 291 pg/ml +/- 35 pg/ml; 442 pg/ml +/- 56 pg/ml vs 287 pg/ml +/- 48 pg/ml, both P < 0.05). (2) The glucose stimulated insulin secretion (GSIS) was impaired in the high-fat-diet rats. 16.7 nmol/L glucose could inhibit the glucagon secretion by the alpha cells of the normal rats, but not of the high-fat-diet rats. (3) The expression of IRc, IRS-1 and IRS-2 in islets was stronger in the peripheral cells (non-insulin secretion cells) than in the center cells (insulin secretion cells). The expression of IRc and IRS-2 was significantly decreased by 28% and 22% respectively in the high-fat-diet rats compared with the normal controls (both P < 0.01).


CONCLUSIONS
High-fat-diet rats have impairment of insulin signal transduction in islet cells, which may contribute to the insulin resistance of islet alpha and beta cells and explain, at least in part, the dysfunction of the islet cells under peripheral IR.
Wu
Yun-hong
YH
Insulin and Diabetes Research Unit, Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China.
Li
Xiu-jun
XJ
Li
Hong-liang
HL
Wang
Yu
Y
Zhang
Xuan-e
XE
Ke
Liu
L
Zhang
Xiang-xun
XX
D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D005934:Glucagon; D011972:Receptor, Insulin