title: In vitro relationship between magnesium and insulin secretion.
abstract: Magnesium, the most abundant intracellular divalent cation, is known to play an essential role in many normal cell functions, such as fluid and electrolyte transport, enzyme activity, and cell proliferation. It is known that magnesium deficiency or hypomagnesaemia induces hyperinsulinism, while hypermagnesaemia inhibits insulin secretion: however, the mechanism controlling the intracellular level of free magnesium and its role in the insulin-secretory mechanism of pancreatic beta cells (RIN m5F cells) are still unclear. Using a fluorescent indicator (mag-fura-2) we have found that the influx of magnesium appears to be voltage-dependent and is sensitive to blockade of the voltage-dependent calcium channel in RIN m5F cells; the efflux of magnesium appears to be voltage- and cyclic AMP-independent. We have observed that depletion of extracellular magnesium potentiates insulin secretion from RIN m5F cells. This finding has led us to speculate on two possible mechanisms through which extracellular magnesium participates in the regulation of insulin secretion: (1) extracellular magnesium may regulate ATP-sensitive potassium channels, and (2) extracellular magnesium may act as a competitive inhibitor of the calcium influx mediated through the voltage-dependent calcium channel. In addition to the role of extracellular magnesium, the changes in the intracellular levels of free magnesium observed during secretagogue-stimulated insulin secretion may alter magnesium-sensitive enzymes or systems, which may play regulatory roles in signal transduction. Elucidation of the role of magnesium in the insulin secretory mechanism will be beneficial for understanding the insulin secretory mechanism of pancreatic beta cells and may be helpful in treating insulin-related abnormalities in patients with hypo- or hypermagnesaemia.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston 77555.
authors.forename: J
authors.initials: J
authors.lastname: Ishizuka
authors.forename: R J
authors.initials: RJ
authors.lastname: Bold
authors.forename: C M
authors.initials: CM
authors.lastname: Townsend
authors.forename: J C
authors.initials: JC
authors.lastname: Thompson
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D005985:Glyceraldehyde / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D015220:Calcium Channels; D007328:Insulin; D005576:Colforsin; D005985:Glyceraldehyde; D011189:Potassium Chloride; D000242:Cyclic AMP; D008274:Magnesium; D002118:Calcium