Renal glucose production during insulin-induced hypoglycemia in humans

Eugenio Cersosimo, Peter Garlick, John Ferretti

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68 Scopus citations

Abstract

We investigated the effects of hypoglycemia on renal glucose production (RGP) and renal glucose uptake (RGU) using arteriovenous balance combined with tracer technique in humans. Our 14 healthy subjects had arterialized hand veins (artery) and renal veins (under fluoroscopy) catheterized after an overnight fast. Systemic and renal glucose kinetics were measured with infusion of [6-2H2]glucose, and renal plasma flow was measured by para- aminohippurate clearance. After a 150-min equilibration period, artery and renal vein samples were obtained between -30 and 0 min, and subjects received a 180-min peripheral insulin infusion (0.250 mU · kg-1 · min-1) with a variable infusion of [6-2H2]dextrose adjusted to maintain plasma glucose at either ~60 mg/dl (hypoglycemic clamp) or ~90 mg/dl (euglycemic clamp). Blood samples were obtained between 150 and 180 min during the study period. Insulin increased from 49 ± 14 to 130 ± 25 (hypoglycemia) and to 102 ± 10 (euglycemia) pmol/l. Glucose decreased from 5.32 ± 0.11 to 3.58 ± 0.07 μmol/ml during hypoglycemia, but it did not change during euglycemia (5.20 ± 0.19 vs. 5.05 ± 0.15 μmol/ml). Endogenous glucose production decreased (9.30 ± 0.70 vs. 5.65 ± 0.50) during euglycemia but not during hypoglycemia (9.80 ± 0.50 vs. 10.25 ± 0.60 μmol · kg-1 · min-1.) During hypoglycemia, net renal glucose output increased from 0.54 ± 0.30 to 2.31 ± 0.40, RGP increased from 1.88 ± 0.70 to 3.65 ± 0.50 (P < 0.05), and RGU did not change (1.34 ± 0.50 vs. 1.34 ± 0.60 μmol · kg-1 · min-1). During euglycemia, renal glucose balance switched from a net output of 0.72 ± 0.20 to a net uptake of 1.70 ± 0.92, RGP decreased from 2.31 ± 0.50 to 1.20 ± 0.58, and RGU increased from 1.59 ± 0.50 to 2.90 ± 0.70 μmol · kg-1 · min-1 (P < 0.05). During hypoglycemia, arterial glucagon increased from 105 ± 6 to 129 ± 8, epinephrine increased from 116 ± 28 to 331 ± 33, norepinephrine increased from 171 ± 9 to 272 ± 9 (all P < 0.05), and renal vein norepinephrine increased from 236 ± 13 to 426 ± 50 (P < 0.001). These data indicate that, in addition to counterregulatory hormones, activation of the autonomic nervous system during hypoglycemia stimulates glucose production by the kidney, which may represent an important additional component of the body's defense against hypoglycemia in humans.

Original languageEnglish (US)
Pages (from-to)261-266
Number of pages6
JournalDiabetes
Volume48
Issue number2
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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