+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Glucagon stimulates expression of the inducible cAMP early repressor and suppresses insulin gene expression in pancreatic beta-cells

, : Glucagon stimulates expression of the inducible cAMP early repressor and suppresses insulin gene expression in pancreatic beta-cells. Diabetes 49(10): 1681-1690

The hormone glucagon is secreted by the alpha-cells of the endocrine pancreas (islets of Langerhans) during fasting and is essential for the maintenance of blood glucose levels by stimulation of hepatic glucose output. Excessive production and secretion of glucagon by the alpha-cells of the islets is a common accompaniment to diabetes. The resulting hyperglucagonemia stimulates hepatic glucose production, thereby contributing to hyperglycemia of diabetes. The reduced insulin secretion in diabetes and resultant failure to suppress glucagon secretion by intra-islet paracrine mechanisms is believed to cause the hypersecretion of glucagon. Here, we report the discovery of a new mechanism by which glucagon suppresses insulin secretion. We show that glucagon, but not glucagon-like peptide 1 (GLP-1), or pituitary adenylyl cyclase-activating peptide (PACAP) specifically induces the expression of the transcriptional repressor inducible cAMP early repressor (ICER) in pancreatic beta-cells, resulting in a repression of the transcriptional expression of the insulin gene. Remarkably, glucagon, GLP-1, and PACAP all stimulate the formation of cAMP to a comparable extent in rat pancreatic islets, but only glucagon activates the expression of ICER and represses insulin gene transcription in beta-cells. These findings lead us to propose that hyperglucagonemia may additionally aggravate the diabetic phenotype via a suppression of insulin gene expression mediated by the transcriptional repressor ICER.


PMID: 11016452

DOI: 10.2337/diabetes.49.10.1681

Other references

Boyce, T.M.; Bloebaum, R.D., 1993: Cortical aging differences and fracture implications for the human femoral neck. Clinical imaging techniques cannot consistently identify individuals at risk for hip fracture. Individual differences in falling likelihood partly account for these inconsistencies, but it is also thought that microscopic bone changes may play a r...

Robbins P.S.; Hessney M.L.; Eckenrode C.J., 1991: Onion allium cepa buccaneer onion maggot delia antiqua meigen onion maggot control 1990. Insecticide & Acaricide Tests : 88

Feffer, M.H., 1961: The influence of affective factors on conceptualization in schizophrenia. Journal of Abnormal and Social Psychology 63: 588-596

Yang, W.Seok.; Stockwell, B.R., 2008: Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. We screened small molecules to identify two compounds, which we named RSL3 and RSL5, that have increased lethality in the presence of oncogenic RAS. Counter screening with biologically active compounds defined aspects of the mechanism of action f...

Mori, A., 2009: Preface. 20th annual workshop on 'Eosinophils in Allergy and Related Diseases' 2008. International Archives of Allergy and Immunology 149 Suppl 1: 1-1

Shepperd, J.A.; Howell, J.L.; Logan, H., 2014: A survey of barriers to screening for oral cancer among rural Black Americans. Research documents a disparity between Black and White Americans in mortality for oral cancer that appears to result in part from behaviors such as lower oral cancer screening among Black Americans. We examined barriers to oral cancer screening am...

Penaloza, L.J., 1991: Boating pressure on Wisconsin's lakes and rivers: results of the 1989-1990 Wisconsin Recreational Boating Study, Phase 1. In 1989, the Wisconsin Department of Natural Resources (DNR) Bureau of Law Enforcement initiated an intensive study of recreational boating in Wisconsin. Objectives were to provide information on boaters' activities and experiences that could...

Pokrovskiĭ, A.V.; Kazanchian, P.O.; Ermoliuk, R.S.; Varava, B.N.; Dan, V.N., 1989: Reconstructive vascular surgery in patients with diabetes mellitus. Presented are the literature data and original research findings in management of atherosclerotic occlusions of major arteries in diabetic patients. Reconstructive surgery in diabetes results in significant anti-ischaemic effect, gangrene localiza...

Scholz, D.A.; Purnell, D.C.; Goldsmith, R.S.; Smith, L.H.; Riggs, B.L.; Arnaud, C.D., 1972: Diagnostic considerations in hypercalcemic syndromes. Medical Clinics of North America 56(4): 941-950

Yang, Y.Y.; Deng, H.C.; Wang, B.H., 1998: The increasing use of anticonvulsants in prophylactic treatment of bipolar disorder. The medical records of patients with bipolar disorders who received prophylactic drug treatments during three time periods from January 1983 to December 1984, January 1988 to December 1989, and from January 1993 to December 1994, were reviewed ret...