Pathogenesis of hypoglycemia in insulinoma patients. Suppression of hepatic glucose production by insulin

R. A. Rizza, M. W. Haymond, C. A. Verdonk, L. J. Mandarino, J. M. Miles, F. J. Service, J. E. Gerich

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


To determine the mechanism by which hyperinsulinemia causes hypoglycemia in insulinoma patients, rates of glucose production and utilization, and circulating levels of insulin, glucagon, alanine, lactate, and glycerol were measured in 6 insulinoma patients during development of fasting hypoglycemia and in 8 normal volunteers studied over an identical interval. Initially, insulinoma patients had a greater plasma insulin (42 ± 9 versus 15 ± 1 μU/ml) and glucagon levels (214 ± 31 versus 158 ± 21 pg/ml) than normal subjects, P < 0.05, but their plasma glucose levels (81 ± 4 mg/dl) and rates of glucose production and utilization (1.71 ± 0.08 and 1.74 ± 0.08 mg/kg . min, respectively) were not significantly different from those of normal subjects (93 ± 2 mg/dl, 1.93 ± 0.11, and 1.92 ± 0.13 mg/kg . min, respectively). During a subsequent 8-h fast, glucose production and glucose utilization decreased in both groups, but more markedly in insulinoma patients. Since glucose utilization exceeded glucose production to a greater extent in insulinoma patients than in normal subjects, plasma glucose decreased to 44 ± 3 mg/dl in insulinoma patients, but only to 84 ± 1 mg/dl in normal subjects (P<0.001). Glucose utilization in insulinoma patients never exceeded that of normal subjects. These results demonstrate that fasting hypoglycemia in the insulinoma patients is usually due to suppression of glucose production rather than to acceleration of glucose utilization, as is widely thought. A direct effect of insulin on the liver is probably responsible, since circulating levels of gluconeogenic precursors are normal and since plasma glucagon increases during development of hypoglycemia in insulinoma patients.

Original languageEnglish (US)
Pages (from-to)377-381
Number of pages5
JournalUnknown Journal
Issue number5
StatePublished - 1981
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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