TY - JOUR
T1 - Obesity is associated with impaired insulin-mediated potassium uptake
AU - DeFronzo, Ralph A.
N1 - Funding Information:
Vol 37. No. 2 (February), 1988: pp 105-108 Experimental Prolocol Each of the obese and control subjects received three euglycemic insulin clamp studies” in which the insulin infusion dose was varied IOO-fold (40,400, and 4,000 mu/m* x min) to span the physiologic and supraphysiologic range of plasma insulin concentrations while maintaining euglycemia. Studies are carried out in random order with 5-to 14-day intervals between the three insulin infusion protocols. All studies were begun at 8 AM following a loto 12-hour overnight fast. Prior to study a catheter was inserted into an antecubital vein for the infusion of all test substances. A second catheter was inserted retrogradely into a hand vein and the hand was placed in a heated box (70°C) in an attermpt to achieve arterialization of the venous blood. All blood samples were drawn from the heated hand catheter. The procedure for performing the insulin clamp study has been described in detail previously.” Briefly, a prime-continuous infusion of insulin is administered to acutely raise and maintain the plasma insulin concentration to the desired hyperinsulinemic plateau for 120 minutes. The plasma glucose concentration is maintained at the basal level by determination of the plasma glucose concentration every five minutes and the periodic adjustment of a variable infusion of a 20% glucose solution based upon a servo-control negative From the Divisions of NephraIogy and Endocrinology/Diabetes. Department of Medicine, Yale University School of Medicine, New Haven, CT. Supported by NIH Grant No. AM24092 and by Clinical Research Center Grant No. RR1 25. Address reprint requests to Ralph A. DeFronzo. MD, 2071 LMP Bldg. Yale-New Haven Hospital, 333 Cedar St, New Haven, CT 06510. o 1988 by Grune & Siratton. Inc. 0026-0495/88/3702-0001$03.00/0 Metabolism, 105 106 feedbackp rincipal.‘*U ndert heses teady-statceo nditionso f constant euglycemiaa ll of the infusedg lucoseis takenu p by cellsa nd,w hen addedt o the rateo f residuahl epaticg lucosep roductions, ervesa s a measureo f total body insulin-mediategdl ucosed isposal.” During the 40 and 400 mu/m’ x min insulinc lamps tudies‘H -3-glucose (New England Nuclear, Boston)w as infusedt o measureg lucose productiona s previouslyd escribedI3. T he tritiatedg lucosein fusion wasg ivena s a prime( 25 PCi) continuousin fusion( 0.25$ Zi/min), starting1 20m inutesb eforet he insulinc lamp.P lasmas amplesf or tritiated glucoses pecific activityI were obtaineda t five-minute intervalso vert he 30m inutesb efores tartingt hei nsulinc lampa nda t five-t o lo-minutei ntervalsd uringt het wo-hourin sulinc lamps tudy. Tritiatedg lucosew as not infusedd uringthe 4,000m u/m’ x min insulinc lamps tudys inceh epaticg lucosep roductionw ass hownt o be completelys uppresseddu ringt he 400m u/m* x min insulinc lamp step.P lasmai nsulina ndp otassiumco ncentrationwse rem easureadt five-to lo-minute intervalso ver the 30-minutep eriodb eforea nd duringt he 120-minutien sulinc lampp eriod. Calculations During the insulinc lamps tudiest he amounto f glucosem etabo-lized by the wholeb ody was determinedb y calculatingt he mean glucosein fusionr atef rom 20 to 120m inutesa nd addingt o this the amounto f residualh epaticg lucosep roduction.T o calculatet he steady-statep lasmag lucosea nd insulin concentrationdsu ring the insulin clamp, the mean of valuesf rom 20 to 120 minutesw as employedT. he basalp lasmap otassiumco ncentratiorne presenttsh e meano f fivev alueso btainedo vert he 30m inutesp rior to startingt he insulinc lamp.
Funding Information:
From the Divisions of NephraIogy and Endocrinology/Diabetes. Department of Medicine, Yale University School of Medicine, New Haven, CT. Supported by NIH Grant No. AM24092 and by Clinical Research Center Grant No. RR1 25. Address reprint requests to Ralph A. DeFronzo. MD, 2071 LMP Bldg. Yale-New Haven Hospital, 333 Cedar St, New Haven, CT 06510. o 1988 by Grune & Siratton. Inc. 0026-0495/88/3702-0001$03.00/0
PY - 1988/2
Y1 - 1988/2
N2 - The ability of insulin to promote extrarenal potassium uptake and to stimulate glucose uptake was examined in eight obese and ten normal weight control subjects. Insulin was infused at three rates to produced plasma insulin concentrations of approximately 100, 1,900, and 19,000 μU/mL. Insulin-mediated potassium, as well as glucose uptake, was diminished during the lowest dose insulin clamp study (100 μU/mL) but could be normalized at pharmacologic plasma insulin concentrations. These results indicate that obese subjects are resistant to the ability of insulin to stimulate potassium uptake by extrarenal tissues. Imparied potassium uptake at physiologic plasma insulin levels, with normalization at supraphysiologic insulin concentrations, is most consistent with a decrease in the number of insulin receptors on insulin target tissues.
AB - The ability of insulin to promote extrarenal potassium uptake and to stimulate glucose uptake was examined in eight obese and ten normal weight control subjects. Insulin was infused at three rates to produced plasma insulin concentrations of approximately 100, 1,900, and 19,000 μU/mL. Insulin-mediated potassium, as well as glucose uptake, was diminished during the lowest dose insulin clamp study (100 μU/mL) but could be normalized at pharmacologic plasma insulin concentrations. These results indicate that obese subjects are resistant to the ability of insulin to stimulate potassium uptake by extrarenal tissues. Imparied potassium uptake at physiologic plasma insulin levels, with normalization at supraphysiologic insulin concentrations, is most consistent with a decrease in the number of insulin receptors on insulin target tissues.
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U2 - 10.1016/S0026-0495(98)90001-4
DO - 10.1016/S0026-0495(98)90001-4
M3 - Article
C2 - 3277011
AN - SCOPUS:0023835576
SN - 0026-0495
VL - 37
SP - 105
EP - 108
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 2
ER -