Furosemide reduces insulin release by inhibition of Cl sup minus and Ca sup 2+ fluxes in. beta. -cells
- Univ. of Umea (Sweden)
The effect of furosemide on insulin release, glucose oxidation, {sup 36}Cl{sup {minus}} fluxes, and {sup 45}Ca{sup 2+} uptake was studied in isolated, {beta}-cell-rich pancreatic islets from ob/ob mice. Low concentrations of furosemide (0.01-0.1 mM) reduced the glucose-induced insulin release, whereas high doses (1-10 mM) increased basal and glucose-induced release. Furosemide at concentrations that reduced glucose-induced insulin release did not affect the islet production of {sup 14}CO{sub 2} from D-(U-{sup 14}C)glucose. The influx rate and equilibrium content of {sup 36}Cl{sup {minus}} were reduced by furosemide, whereas the basal and glucose-stimulated {sup 36}Cl{sup {minus}} efflux rates were unaffected. The glucose-induced uptake of {sup 45}Ca{sup 2+} was inhibited by furosemide. It is suggested that the diabetogenic action of furosemide may be due, at least in part, to direct inhibition of insulin release from the pancreatic {beta}-cells. This may be caused primarily by inhibition of an inwardly directed Cl{sup {minus}} pump, leading to a reduced transmembrane electrochemical gradient for chloride in the {beta}-cells. This reduced gradient in combination with unaltered Cl{sup {minus}} permeability may lead to decreased total outward Cl{sup {minus}} transport, a factor associated with stimulated calcium uptake and insulin release.
- OSTI ID:
- 6037117
- Journal Information:
- American Journal of Physiology; (USA), Vol. 255:5; ISSN 0002-9513
- Country of Publication:
- United States
- Language:
- English
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CALCIUM 45
MEMBRANE TRANSPORT
CHLORINE 36
DIURETICS
BIOLOGICAL EFFECTS
INSULIN
SECRETION
CARBON 14 COMPOUNDS
DIABETES MELLITUS
GLUCOSE
KIDNEYS
OXIDATION
PERMEABILITY
PHYSIOLOGY
ALDEHYDES
ALKALINE EARTH ISOTOPES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CARBOHYDRATES
CHEMICAL REACTIONS
CHLORINE ISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE DISEASES
EVEN-ODD NUCLEI
HEXOSES
HORMONES
INTERMEDIATE MASS NUCLEI
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
METABOLIC DISEASES
MONOSACCHARIDES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
RADIOISOTOPES
SACCHARIDES
YEARS LIVING RADIOISOTOPES
551001* - Physiological Systems- Tracer Techniques