+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Impaired glucose-stimulated insulin secretion, enhanced intraperitoneal insulin tolerance, and increased beta-cell mass in mice lacking the p110gamma isoform of phosphoinositide 3-kinase



Impaired glucose-stimulated insulin secretion, enhanced intraperitoneal insulin tolerance, and increased beta-cell mass in mice lacking the p110gamma isoform of phosphoinositide 3-kinase



Endocrinology 145(9): 4078-4083



Phosphoinositide 3-kinase (PI3 kinase) has been implicated in G protein-coupled receptor regulation of pancreatic beta-cell growth and glucose-stimulated insulin secretion. The G protein-activated p110gamma isoform of PI3 kinase was detected in insulinoma cells, mouse islets, and human islets. In 7- to 10-wk-old mice, knockout of p110gamma reduced the plasma insulin response to ip glucose injection and impaired first and second phase glucose-stimulated insulin secretion from pancreata perfused ex vivo. The p110gamma -/- mice responded to preinjection with the glucagon-like peptide-1 receptor agonist exendin 4, such that plasma glucose and insulin responses to ip glucose injection were not different from wild types. Mice lacking p110gamma were not diabetic and were only slightly glucose intolerant (ip glucose injection) compared with wild types, in part due to enhanced responsiveness to insulin as determined by an ip insulin tolerance test. Despite severely reduced insulin secretion in these animals, the p110gamma -/- mice had greater pancreatic insulin content, and an increased beta-cell mass due to beta-cell hypertrophy. These surprising results suggest that the G protein-coupled p110gamma isoform of PI3 kinase is not central to the development or maintenance of sufficient beta-cell mass but positively regulates glucose-stimulated insulin secretion.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012185441

Download citation: RISBibTeXText

PMID: 15231713

DOI: 10.1210/en.2004-0028


Related references

Loss of mPer2 increases plasma insulin levels by enhanced glucose-stimulated insulin secretion and impaired insulin clearance in mice. Febs Letters 586(9): 1306-1311, 2012

Insulin resistance causes increased beta-cell mass but defective glucose-stimulated insulin secretion in a murine model of type 2 diabetes. Diabetologia 49(1): 90-99, 2006

Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice. Embo Journal 22(15): 3844-3854, 2003

Islet dysfunction in insulin resistance involves impaired insulin secretion and increased glucagon secretion in postmenopausal women with impaired glucose tolerance. Diabetes Care 23(5): 650-657, 2000

Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proceedings of the National Academy of Sciences of the United States of America 97(12): 6874-6879, 2000

Transgenic mice expressing a dominant negative Akt in beta cells have normal cell mass, impaired glucose tolerance, decreased insulin secretory responses, and enhanced susceptibility to fat feeding and streptozotocin -induced diabetes. Diabetes 52(Suppl. 1): A42, 2003

Impaired insulin secretion in vivo but enhanced insulin secretion from isolated islets in pancreatic beta cell-specific vascular endothelial growth factor-A knock-out mice. Diabetologia 50(2): 380-389, 2007

The contribution of muscle phosphofructokinase isoform to insulin secretion from the pancreatic beta-cell and to insulin-stimulated glucose disposal by the muscle. Diabetes & Metabolism 29(Hors serie 2): 4S76, 2003

Aqueous fraction of Beta vulgaris ameliorates hyperglycemia in diabetic mice due to enhanced glucose stimulated insulin secretion, mediated by acetylcholine and GLP-1, and elevated glucose uptake via increased membrane bound GLUT4 transporters. Plos one 10(2): E0116546, 2015

Increased insulin secretion and glucose tolerance in mice lacking islet amyloid polypeptide (amylin). Biochemical and Biophysical Research Communications 250(2): 271-277, 1998

Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes study. Diabetes Care 26(3): 868-874, 2003

Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase beta-cell mass in fetal sheep. 2013

Increased amino acid supply potentiates glucose stimulated insulin secretion but does not increase beta cell mass in fetal sheep. 2013

CART knock out mice have impaired insulin secretion and glucose intolerance, altered beta cell morphology and increased body weight. Regulatory Peptides 129(1-3): 203-211, 2005

Increased uncoupling protein-2 levels in beta-cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action. Diabetes 50(6): 1302-1310, 2001