Effects of palmitate on insulin secretion and exocytotic proteins in islets of diabetic Goto-Kakizaki rats

CG Östenson, J Chen, L Sheu, HY Gaisano - Pancreas, 2007 - journals.lww.com
CG Östenson, J Chen, L Sheu, HY Gaisano
Pancreas, 2007journals.lww.com
Objectives: We examined how lipotoxicity contributes to pancreatic beta-cell secretory
dysfunction. Methods: Effects of palmitate (0.2 mmol/L) were assessed on insulin secretion
and soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic
machinery in isolated pancreatic islets of type 2 diabetic Goto-Kakizaki (GK) rats and control
Wistar (W) rats. Results: One-day palmitate treatment enhanced basal glucose (3.3 mmol/L)-
mediated insulin release 5-fold in W and 3.3-fold in GK islets, but had no effect at high …
Abstract
Objectives:
We examined how lipotoxicity contributes to pancreatic beta-cell secretory dysfunction.
Methods:
Effects of palmitate (0.2 mmol/L) were assessed on insulin secretion and soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic machinery in isolated pancreatic islets of type 2 diabetic Goto-Kakizaki (GK) rats and control Wistar (W) rats.
Results:
One-day palmitate treatment enhanced basal glucose (3.3 mmol/L)-mediated insulin release 5-fold in W and 3.3-fold in GK islets, but had no effect at high glucose (16.7 mmol/L) on W islets while enhancing GK islet insulin release 2-fold. After 3-day palmitate treatment, high-glucose-induced insulin release in W islets was reduced (by 69%), whereas in GK islets, it increased 2-fold. Insulin response to arginine was reduced in both islet types, but more so in GK islets. Exocytotic proteins (syntaxin 1A, VAMP-2, SNAP-25, nSec1) were reduced in GK islets by 56% to 69% compared with W islets. In W islets, palmitate treatment caused no changes in the levels of these proteins but increased actin levels. In GK islets, whereas 1-day palmitate treatment had no effect, 3-day treatment further reduced SNAP-25 and nSec1 levels.
Conclusions:
Lipotoxic-induced secretory insufficiency in normal islets may be attributed to lack of compensatory increase in levels of exocytotic proteins and/or excess actin. However, in GK islets, palmitate treatment moderately enhanced insulin secretion, likely by acting on proximal metabolic pathways capable of compensating for the defective soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic machinery. These results were different from prolonged glucose treatment we previously reported, indicating differences between glucotoxic and lipotoxic actions on the insulin secretory machinery.
Lippincott Williams & Wilkins