Chronic Antidiabetic Actions of Leptin: Evidence From Parabiosis Studies for a CNS-Derived Circulating Antidiabetic Factor.

Abstract

We used parabiosis to determine whether the central nervous system (CNS)-mediated antidiabetic effects of leptin are mediated by release of brain-derived circulating factors. Parabiosis was surgically induced at 4 weeks of age, and an intracerebroventricular (ICV) cannula was placed in the lateral cerebral ventricle at 12 weeks of age for ICV infusion of leptin or saline vehicle. Ten days after surgery, food intake, body weight, and blood glucose were measured for 5 consecutive days, and insulin-deficiency diabetes was induced in all rats by a single streptozotocin (STZ) injection (40 mg/kg). Five days after STZ injection, leptin or vehicle was infused ICV for 7 days, followed by 5-day recovery period. STZ increased blood glucose and food intake. Chronic ICV leptin infusion restored normoglycemia in leptin-infused rats while reducing blood glucose by ∼27% in conjoined vehicle-infused rats. This glucose reduction was caused mainly by decreased hepatic gluconeogenesis. Chronic ICV leptin infusion also reduced net cumulative food intake and increased GLUT4 expression in skeletal muscle in leptin/vehicle compared with vehicle/vehicle conjoined rats. These results indicate that leptin's CNS-mediated antidiabetic effects are mediated, in part, by release into the systemic circulation of leptin-stimulated factors that enhance glucose utilization and reduce liver gluconeogenesis.

• Authors: Alexandre A da Silva, John E Hall, Xuemei Dai, Zhen Wang, Mateus C Salgado, Jussara M do Carmo
• Journal: Diabetes (Diabetes) Vol. 70 Issue 10 Pg. 2264-2274 (10 2021) ISSN: 1939-327X [Electronic] United States
• PMID: 34344788 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2021 by the American Diabetes Association.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Leptin
• Streptozocin

Topics

• Animals
• Blood Glucose (drug effects, metabolism)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Central Nervous System (drug effects, metabolism)
• Diabetes Mellitus, Experimental (chemically induced, metabolism, pathology)
• Drinking (drug effects)
• Eating (drug effects)
• Hypoglycemic Agents (blood, metabolism, pharmacology)
• Infusions, Intraventricular
• Insulin (blood)
• Leptin (administration & dosage, blood, metabolism, pharmacology)
• Male
• Parabiosis
• Rats
• Rats, Inbred Lew
• Streptozocin