Furosemide reduces insulin release by inhibition of Cl sup minus and Ca sup 2+ fluxes in. beta. -cells

Journal Article · Tue Nov 01 00:00:00 EST 1988 · American Journal of Physiology; (USA)

OSTI ID:6037117

Sandstroem, P E; Sehlin, J ^[1]

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1. 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

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
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