[Effect of lipid infusion on the function of islet beta cells and gene expression of insulin signal transduction system].
OBJECTIVE
To study the changes and mechanism of the function of islet beta cells and insulin signal transduction molecules after lipid infusion.


METHODS
Twenty five SD rats were randomly divided into 2 groups, FFA group and NS group. Catheters were implanted under pentobarbital anesthesia in the right atrium via the jugular vein and the left carotid artery. A technique for a 48 h infusion in unrestrained rats was used for triglyceride and heparin or saline infusion. The infusion period started on day 2 after surgery. After 48 h infusion, we determined fasting serum insulin (Ins), free fat acid (FFA) in the blood. The glucose infusion rate (GIR) was measured by hyperinsulinemia euglycemic clamp to evaluate the peripheral insulin resistance. The ivgtt and islet cell perifusion was conducted to evaluate the function of islet beta cells. The rats in the two groups were sacrificed, and the pancreatic islets were isolated and collected. The expressions of insulin receptor substrate-1(IRS-1), insulin receptor substrate-2 (IRS-2) glucose transporter-2 (Glut-2) gene in islets and IRS-1, IRS-2 in muscle were detected by real-time PCR.


RESULTS
(1) The serum FFA and insulin concentrations of blood in FFA group were higher than in NS group (P<0.05). (2) The GIR was decreased significantly in FFA group compared with that in NS group (P<0.05). (3) The glucose stimulated insulin secretion increased in the FFA group. (4) The gene expression of IRS-1 in muscle was significantly decreased by 87.7% in FFA group, and the expression of IRS-2 was decreased by 50.7% (all P<0.05). The gene expression of IRS-1 in islets was significantly increased by 29.3% (P<0.05), and the expressions of IRS-2, Glut-2 were increased by 345.1% and 536.4% respectively, in FFA group (all P<0.01).


CONCLUSIONS
Lipid infusion in short time increased the secretion of insulin and impaired expression of insulin signal transduction molecules in muscle but it also increased the expression of insulin signal transduction molecules in islet beta cells.
Wang
Bing
B
Postgraduate School, Peking Union Medical College, Beijing 100029, China.
Li
Hong-liang
HL
Yang
Wen-ying
WY
Xiao
Jian-zhong
JZ
Du
Rui-qin
RQ
Bai
Xiu-ping
XP
Pan
Lin
L
D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
D005230:Fatty Acids, Nonesterified; D007328:Insulin