Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats

S. J. Koopmans, B. Leighton, R. A. DeFronzo

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Sensory neuropeptides, released from the peripheral nervous system, might modulate glucose homeostasis by antagonizing insulin action. The effects of de-afferentation of functional small diameter unmyelinated C- fibres (sensory nerves) on in vivo insulin-mediated intracellular glucose metabolism were investigated by using euglycaemic insulin (6 and 18 mU/kg.min) clamps with [3-3H]-glucose infusion in 24 adult rats, treated neonatally with either capsaicin (CAP) (50 mg/kg) or vehicle (CON). Following the clamp, skeletal muscle groups, liver and adipose tissue were freeze- clamped. At plasma insulin levels of approximately 90 mU/l, CAP-rats showed a 21% increase in whole body glucose uptake compared with CON (24.4±1.6 vs 20.1±0.8 mg/kg·min, p < 0.02), which was paralleled by a 20 % increase in whole body glycolysis (12.6 ± 0.8 vs 10.5 ± 0.5 mg/ kg.min p < 0.05) (concentration of 3H2O in plasma). Whole body skeletal muscle glycogenesis was increased by 80% in CAP-rats (5.7±0.7 vs 3.l± 0.7 mg/kg · min, p < 0.05) with increased muscle glycogen synthase activity. Whole body (muscle, liver and adipose tissue combined) de novo lipogenesis also was increased in CAP-rats compared with CON (0.69 ± 0.10 vs 0.44 ± 0.06 mg/kg · min, p < 0.05) (incorporation of [3-3H]-glucose counts into glycogen or fat). Hepatic glucose production was lower in CAP-rats compared with CON (0.6±0.6 vs 2.1 ± 0.7 mg/kg · min, p < 0.05). Plasma glucagon, corticosterone, epinephrine and norepinephrine levels were reduced in CAP-rats: 43±2 compared with 70±6 pg/ml, 855±55 compared with 1131±138 nmol/l, 513 ± 136 compared with 1048 ± 164 pmol/l and 928 ± 142 compared with 1472 ± 331 pmol/l, respectively, p < 0.05. At plasma insulin levels of approximately 400 mU/l, CAP-rats showed no differences in peripheral and hepatic insulin action compared with CON. We conclude that the removae of endogenous sensory neuropeptides, by de- afferentation of capsaicin-sensitive sensory nerves, increases in vivo insulin sensitivity, but not responsiveness: 1) primarily through an increased sensitivity of skeletal muscle glycogen synthesis to insulin; 2) through a reduction in the levels of counter-regulatory hormones, thereby creating a milieu which favours overall in vivo insulin sensitivity with respect to glucose uptake, glucose production, glycolysis, glycogenesis and lipogenesis.

Original languageEnglish (US)
Pages (from-to)813-820
Number of pages8
JournalDiabetologia
Volume41
Issue number7
DOIs
StatePublished - 1998

Keywords

  • Counter-regulatory hormones
  • Glycogenesis
  • Glycolysis
  • Insulin sensitivity
  • Lipogenesis
  • Sensory nerves

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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