Glucose induces insulin release and a rise in cytosolic calcium concentration in a transplantable rat insulinoma

Endocrinology. 1986 Dec;119(6):2502-7. doi: 10.1210/endo-119-6-2502.

Abstract

An important role for calcium in the cellular events leading to insulin secretion is supported by many studies. However, simultaneous measurements of changes in intracellular free Ca2+ concentrations [( Ca2+]i) and insulin release in response to secretagogues have not been performed. Using cells isolated from a glucose-responsive insulinoma, changes in [Ca2+]i were measured with the fluorescent calcium probe quin2. With the nutrient secretagogues glucose (30 mM) and D,L-glyceraldehyde (GA; 20 mM), [Ca2+]i increased slowly, reaching a peak approximately 15 min after addition of the stimulus, while KCl (25 mM) and carbachol (2 mM) led to a rapid but transient increase in [Ca2+]i. Glucose increased [Ca2+]i from 104 +/- 6 (mean +/- SEM) to 248 +/- 31 mM (n = 13), and GA caused a rise in [Ca2+]i from 96 +/- 6 to 280 +/- 39 nM (n = 4). KCl and carbachol caused a rise from 107 +/- 6 to 184 +/- 5 nM and from 98 +/- 5 to 157 +/- 5 nM, respectively (n = 5 each). When insulin release was measured simultaneously with changes in [Ca2+]i and compared to unstimulated cells, the following results were obtained. During the first 5 min of stimulation, high glucose caused a 90 +/- 12% increase in insulin release and a 72 +/- 11% rise in [Ca2+]i (n = 5). GA evoked a 122 +/- 30% increase in insulin secretion, with a 82 +/- 17% rise in [Ca2+]i (n = 3). Both KCl and carbachol caused a 58 +/- 9% increase in insulin release, with 7 +/- 4% and 50 +/- 2% rises in [Ca2+]i, respectively (n = 4 each). Insulin release was also measured in a perifusion system. It was shown that glucose (30 mM), GA (20 mM), and alpha-ketoisocaproate (30 mM) caused a biphasic release of insulin, while KCl (25 mM) and carbachol (2 mM) caused a monophasic release. The results show that [Ca2+]i increases during the stimulation of insulin secretion when measured simultaneously on the same beta-cells. However, while these changes coincide, a simple direct quantitative relationship between insulin release and the rise in [Ca2+]i could not be demonstrated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma, Islet Cell / metabolism*
  • Aminoquinolines
  • Animals
  • Calcium / metabolism*
  • Carbachol / pharmacology
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Glucose / pharmacology*
  • Glyceraldehyde / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulinoma / metabolism*
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / metabolism
  • Potassium Chloride / pharmacology
  • Rats
  • Secretory Rate / drug effects
  • Time Factors

Substances

  • Aminoquinolines
  • Insulin
  • Glyceraldehyde
  • Potassium Chloride
  • Quin2-acetoxymethyl ester
  • Carbachol
  • Glucose
  • Calcium