Physiology and pathophysiology of glucagon

Roger H Unger, L. Orci

Research output: Contribution to journalReview articlepeer-review

189 Scopus citations


The islets of Langerhans perform the vital function of fuel distribution. The biologic actions of its two major secretory products, insulin and glucagon, endow it with the abilities to direct the storage of exogenous fuels in the insulin sensitive tissues of the body and, when required, to retrieve and redistribute them at rates precisely titrated to prevailing needs. The opposing and counterbalancing actions of the two hormones make possible wide changes in nutrient flux with but minor changes in their concentration. Because in most higher life forms glucose is, under normal circumstances, the primary cerebral fuel, glucoregulation is the primary functional concern of the islet cell system. The A and B cells are exquisitely perceptive glucose sensors, responding promptly and appropriately to changes in glucose need and availability. Although they also respond to changes in the concentration of other substrates and hormones and to the autonomic nervous system, the ambient glucose concentration is the dominant controlling force of the bicellular unit and normally will determine the magnitude of the response to influential signals other than glucose. In the moment to moment sense, insulin and glucagon can be viewed as directing the metabolic ''traffic'': i.e., the flux of glucose, amino acids, fatty acids, and ketones. In the long term sense, they may be regarded as determining the direction of metabolism toward anabolism or catabolism. Clearly, the proper function of this organ is vital to health and to survival and its improper function may result in disorders to fuel delivery of which diabetes mellitus and hypoglycemia are familiar examples.

Original languageEnglish (US)
Pages (from-to)778-826
Number of pages49
JournalPhysiological reviews
Issue number4
StatePublished - Jan 1 1976

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)


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