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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Starke, A. Grundy, S. Mcgarry, J. D. Unger, R. H. |
| Abstract | In insulin-deprived alloxan-induced diabetic dogs with severe hyperglycemia and marked hyperglucagonemia, glucagon was not suppressed by intravenous infusion of glucose at a progressively increasing rate up to 24 mg/kg of body weight per min. However, when the hyperglycemia was corrected by phloridzin, a blocker of renal tubular glucose reabsorption, the hyperglucagonemia was readily suppressed by as little as 2 mg of glucose per kg/min. Direct perfusion of phloridzin into the isolated pancreas of nondiabetic dogs had no effect on the in vitro glucagon response to increments in glucose. However, in pancreata isolated from dogs whose glucose levels had been lowered by phloridzin pretreatment, in vitro glucagon suppression in response to glucose increments was more than twice that of controls. This enhancing effect of phloridzin treatment was completely abolished by giving an intravenous infusion of glucose for the 5 hr prior to surgery for isolation of the pancreas. It is concluded that (i) alpha cells have a glucose-sensing system that is independent of insulin and beta cells, and (ii) this system is reversibly attenuated by hyperglycemia. Thus, hyperglycemia, a metabolic consequence of islet cell dysfunction, may be a self-exacerbating inducer of further islet cell dysfunction, a possibility with implications for human diabetes. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 82 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1985-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Diabetes Mellitus, Experimental Drug Therapy Glucagon Physiology Hyperglycemia Islets Of Langerhans Physiopathology Phlorhizin Therapeutic Use Animals Glucose Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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