Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: Reversal by insulin

Peter J. Havel, Janet Y. Uriu-Hare, Tina Liu, Kimber L. Stanhope, Judith S. Stern, Carl L. Keen, Bo Ahrén

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Abstract

Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes was induced in rats with streptozotocin (STZ; 40 mg · kg-1 · day-1 x 2 days) to examine the effect of insulin-deficient diabetes and insulin treatment on circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats were all <0.4 ng/ml versus 4.9 ± 0.9 ng/ml in control animals (P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk, which reduced hyperglycemia by ~50%, plasma leptin was 2.1 ± 0.6 ng/ml, whereas leptin concentrations were 6.0 ± 1.6 ng/ml in insulin-implanted rats receiving supplemental injections of insulin for 4 days to normalize plasma glucose (P < 0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at biweekly intervals during 12 wk of diabetes. In rats treated with insulin implants, plasma leptin concentrations were inversely proportional to glycemia (r = -0.64; P < 0.0001) and unrelated to body weight (P = 0.40). In a third experiment, plasma leptin concentrations were examined very early after the induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased from 480 ± 30 to 130 ± 10 pM (P < 0.0001), plasma glucose increased from 7.0 ± 0.2 to 24.8 ± 0.5 mM, and plasma leptin decreased from 3.2 ± 0.2 to 1.2 ± 0.1 ng/ml (Δ = -63 ± 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days, glucose decreased to 11.7 ± 3.9 mM and leptin increased from 0.5 ± 0.1 to 2.9 ± 0.6 ng/ml (P < 0.01) without an effect on epididymal fat weight. The change of leptin was correlated with the degree of glucose lowering (r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces rapid and sustained decreases of leptin that are not solely dependent on weight loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that decreased glucose transport into adipose tissue may contribute to decreased leptin production in insulin-deficient diabetes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume274
Issue number5 43-5
StatePublished - 1998

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Streptozocin
Leptin
Insulin
Glucose
Injections
Hyperglycemia
Adipose Tissue
Weight Loss
Fats
Body Weight

Keywords

  • C-peptide
  • Epididymal fat
  • Food intake
  • Glucose

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats : Reversal by insulin. / Havel, Peter J.; Uriu-Hare, Janet Y.; Liu, Tina; Stanhope, Kimber L.; Stern, Judith S.; Keen, Carl L.; Ahrén, Bo.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 274, No. 5 43-5, 1998.

Research output: Contribution to journalArticle

Havel, Peter J. ; Uriu-Hare, Janet Y. ; Liu, Tina ; Stanhope, Kimber L. ; Stern, Judith S. ; Keen, Carl L. ; Ahrén, Bo. / Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats : Reversal by insulin. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 1998 ; Vol. 274, No. 5 43-5.
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AU - Stern, Judith S.

AU - Keen, Carl L.

AU - Ahrén, Bo

PY - 1998

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N2 - Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes was induced in rats with streptozotocin (STZ; 40 mg · kg-1 · day-1 x 2 days) to examine the effect of insulin-deficient diabetes and insulin treatment on circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats were all <0.4 ng/ml versus 4.9 ± 0.9 ng/ml in control animals (P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk, which reduced hyperglycemia by ~50%, plasma leptin was 2.1 ± 0.6 ng/ml, whereas leptin concentrations were 6.0 ± 1.6 ng/ml in insulin-implanted rats receiving supplemental injections of insulin for 4 days to normalize plasma glucose (P < 0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at biweekly intervals during 12 wk of diabetes. In rats treated with insulin implants, plasma leptin concentrations were inversely proportional to glycemia (r = -0.64; P < 0.0001) and unrelated to body weight (P = 0.40). In a third experiment, plasma leptin concentrations were examined very early after the induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased from 480 ± 30 to 130 ± 10 pM (P < 0.0001), plasma glucose increased from 7.0 ± 0.2 to 24.8 ± 0.5 mM, and plasma leptin decreased from 3.2 ± 0.2 to 1.2 ± 0.1 ng/ml (Δ = -63 ± 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days, glucose decreased to 11.7 ± 3.9 mM and leptin increased from 0.5 ± 0.1 to 2.9 ± 0.6 ng/ml (P < 0.01) without an effect on epididymal fat weight. The change of leptin was correlated with the degree of glucose lowering (r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces rapid and sustained decreases of leptin that are not solely dependent on weight loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that decreased glucose transport into adipose tissue may contribute to decreased leptin production in insulin-deficient diabetes.

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KW - C-peptide

KW - Epididymal fat

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