Ethanol acutely stimulates islet blood flow, amplifies insulin secretion, and induces hypoglycemia via nitric oxide and vagally mediated mechanisms

Endocrinology. 2008 Jan;149(1):232-6. doi: 10.1210/en.2007-0632. Epub 2007 Oct 4.


Hypoglycemia induced by alcohol ingestion is a well-known problem in diabetic patients. However, the mechanisms underlying this phenomenon have largely remained elusive. Because insulin secretion in vivo can be rapidly tuned by changes in pancreatic microcirculation, we evaluated the influence of acute alcohol administration on pancreatic islet blood flow (IBF), and dynamic changes in insulin secretion and glycemia in the rat. Ethanol (10%) or saline was iv injected as a bolus into Wistar rats, yielding serum ethanol concentrations of approximately 8 mmol/liter. Measurements of pancreatic blood flow (PBF) were performed by a microsphere technique in combination with a freeze-thawing technique after 10-min injection. Ethanol preferentially and significantly increased pancreatic IBF approximately 4-fold, whereas not influencing whole PBF. The alcohol also augmented late-phase insulin secretion and induced late hypoglycemia upon ip glucose tolerance tests. The nitric oxide synthase inhibitor N-w-nitro-L-arginine methyl ester and atropine prevented the increased pancreatic IBF, enhanced insulin secretion, and hypoglycemia evoked by ethanol. Thus, our findings demonstrate that ethanol acutely exerts substantial influences on pancreatic microcirculation by evoking a massive redistribution of PBF from the exocrine into the endocrine part via mechanisms mediated by nitric oxide and vagal stimuli, augmenting late-phase insulin secretion, and thereby evoking hypoglycemia. This effect may in part underlie the well-known hypoglycemic properties of alcohol in diabetic patients or in alcoholics with hepatic failure.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Blood Glucose / drug effects
  • Enzyme Inhibitors / pharmacology
  • Ethanol / pharmacology*
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced*
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / blood supply*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide / physiology*
  • Parasympatholytics / pharmacology
  • Rats
  • Rats, Wistar
  • Regional Blood Flow / drug effects
  • Time Factors
  • Vagus Nerve / drug effects
  • Vagus Nerve / metabolism
  • Vagus Nerve / physiology*


  • Blood Glucose
  • Enzyme Inhibitors
  • Insulin
  • Parasympatholytics
  • Nitric Oxide
  • Ethanol
  • Atropine
  • NG-Nitroarginine Methyl Ester