Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 294, Issue 2, Pages E217-E229Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00474.2007
Keywords
transgenic mice; glucose tolerance; insulin tolerance
Categories
Funding
- NCRR NIH HHS [P41 RR000954-30, P41 RR000954, P41 RR 00954] Funding Source: Medline
- NIDDK NIH HHS [R01 DK048494, P60 DK020579-269005, P60 DK020595, P60 DK 20579, P30 DK056341, P30 DK020595, R37 DK 34388, P60 DK020579, DK 48494, P30 DK056341-069003, DK 20595, R37 DK034388-23, P30 DK 56341, R37 DK034388] Funding Source: Medline
- NIGMS NIH HHS [P41 GM103422] Funding Source: Medline
Ask authors/readers for more resources
Studies with genetically modified insulinoma cells suggest that group VIA phospholipase A(2) (iPLA(2)beta) participates in amplifying glucose-induced insulin secretion. INS-1 insulinoma cells that overexpress iPLA(2)beta, for example, exhibit amplified insulin-secretory responses to glucose and cAMP-elevating agents. To determine whether similar effects occur in whole animals, we prepared transgenic (TG) mice in which the rat insulin 1 promoter (RIP) drives iPLA(2)beta overexpression, and two characterized TG mouse lines exhibit similar phenotypes. Their pancreatic islet iPLA(2)beta expression is increased severalfold, as reflected by quantitative PCR of iPLA(2)beta mRNA, immunoblotting of iPLA(2)beta protein, and iPLA(2)beta enzymatic activity. Immunofluorescence microscopic studies of pancreatic sections confirm iPLA(2)beta overexpression in RIP-iPLA(2) beta-TG islet beta-cells without obviously perturbed islet morphology. Male RIP-iPLA(2)beta-TG mice exhibit lower blood glucose and higher plasma insulin concentrations than wild-type (WT) mice when fasting and develop lower blood glucose levels in glucose tolerance tests, but WT and TG blood glucose levels do not differ in insulin tolerance tests. Islets from male RIP-iPLA(2)beta-TG mice exhibit greater amplification of glucose-induced insulin secretion by a cAMP-elevating agent than WT islets. In contrast, islets from male iPLA(2)beta-null mice exhibit blunted insulin secretion, and those mice have impaired glucose tolerance. Arachidonate incorporation into and the phospholipid composition of RIP-iPLA(2)beta-TG islets are normal, but they exhibit reduced Kv2.1 delayed rectifier current and prolonged glucose-induced action potentials and elevations of cytosolic Ca2+ concentration that suggest a molecular mechanism for the physiological role of iPLA(2)beta to amplify insulin secretion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available