Correction of hyperglycemia with phloridzin restores the glucagon response to glucose in insulin-deficient dogs: Implications for human diabetes

A. Starke, Scott M Grundy, J. D. McGarry, Roger H Unger

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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 of 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 implication for human diabetes.

Original languageEnglish (US)
Pages (from-to)1544-1546
Number of pages3
JournalProceedings of the National Academy of Sciences of the United States of America
Volume82
Issue number5
DOIs
StatePublished - 1985

ASJC Scopus subject areas

  • General

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