Role of glucose in IRS signaling in rat pancreatic islets: specific effects and interplay with insulin.
We investigated the possible interplay between insulin and glucose signaling pathways in rat pancreatic beta-cell with a special focus on the role of glucose in IRS signaling in vivo. Three groups of rats were constituted by combining simultaneous infusion during 48 h either of glucose and/or insulin, or glucose+diazoxide: Hyperglycemic-Hyperinsulinemic (HGHI), euglycemic-Hyperinsulinemic (eGHI), Hyperglycemic-euinsulinemic (HGeI). Control rats were infused with 0,9%NaCl. In HGHI and HGeI rats plasma glucose levels were maintained at 20-22 mmol/l. In eGHI rats, plasma glucose was not different from that of controls, whereas plasma insulin was much higher than in controls. In HGHI rats, IRS-2 mRNA expression, total protein and phosphorylated protein amounts were increased compared to controls. In HGeI rats, only IRS-2 mRNA expression was increased. No change was observed in eGHI rats whatever the parameter considered. In all groups, mRNA concentration of IRS-1 was similar to that of controls. The quantity of total and phosphorylated IRS-1 protein was dramatically increased in HGHI rats and to a lesser extent in eGHI rats. Neither mRNA nor IRS-1 protein expression were modified in HGeI rats. The data suggest that glucose and insulin play at once a specific and a complementary role in islet IRSs signaling. Especially, glucose stimulates IRS-2 mRNA expression whatever the insulin status and independently of the secretory process. The differential regulation of IRS-1 and IRS-2 expressions is in agreement with their supposed different involvement in the control of beta-cell growth and function.
Paris
Maryline
M
Laboratoire de Physiopathologie de la Nutrition, Université Paris 7, Paris, France.
Bernard-Kargar
Catherine
C
Vilar
José
J
Kassis
Nadim
N
Ktorza
Alain
A
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000097:blood*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger