Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic, insulin-deficient nonobese Akita mice and leptin-deficient obese ob/ob mice

Peptides
Naohiko UenoS P Kalra

Abstract

We have tested the hypothesis that sustained leptin action in the hypothalamus alone can engender and maintain euglycemia in wild type mice and in two monogenic diabetic models, the insulin-deficient nonobese Akita mice and the hyperinsulinemic leptin-deficient obese, ob/ob mice. A single intracerebroventricular injection of recombinant adeno-associated virus vector encoding leptin (rAAV-lep) enhanced leptin transgene expression in the hypothalamus without any evidence of leptin leakage to the peripheral circulation, and promptly reinstated euglycemia that persisted along with severe insulinopenia in all three genotypes through the 7-week period of observation. A comparative evaluation of known etiologic factors of hyperglycemia showed that this long-term benefit on glucose homeostasis was not due to diminished energy consumption, weight and adiposity, but was conferred by at least two mechanisms operating simultaneously, enhanced glucose metabolism to meet the demand for the rAAV-lep induced increased non-shivering thermogenesis mediated by brown adipose tissue and insulin hypersensitivity. These findings endorse the hypothesis that increased leptin action locally in the hypothalamus can impose euglycemia independent of pancre...Continue Reading

References

Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·G ChenR H Unger
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·M ShimabukuroR H Unger
Nov 13, 1998·The Journal of Biological Chemistry·L LiuL Rossetti
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·J SeufertJ F Habener
May 14, 1999·The Journal of Clinical Endocrinology and Metabolism·K HanakiS A Arslanian
Aug 3, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·H DhillonP S Kalra
Mar 29, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shuji HidakaToshiie Sakata
Jun 8, 2004·The Journal of Clinical Endocrinology and Metabolism·Katie WynneSteve Bloom
Aug 24, 2004·Endocrinology·Thierry Alquier, Barbara B Kahn
Jan 22, 2005·Science·Mitchell A Lazar
May 10, 2005·The Proceedings of the Nutrition Society·Timothy J BartnessMichelle T Foster
Jul 22, 2005·Nature·Deborah M Muoio, Christopher B Newgard

❮ Previous
Next ❯

Citations

Mar 28, 2012·Journal of Diabetes Investigation·Heather C DenrocheTimothy J Kieffer
Dec 9, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Ashwani MalhotraLeonard G Meggs
Jun 3, 2011·The Journal of Clinical Investigation·Laurent Gautron, Joel K Elmquist
Apr 9, 2013·Indian Journal of Endocrinology and Metabolism·Satya P Kalra
Apr 9, 2013·Indian Journal of Endocrinology and Metabolism·Yasuhiko MinokoshiShiki Okamoto
Aug 23, 2011·Journal of Biosciences·Wing-Fu Lai
Aug 10, 2010·Expert Opinion on Biological Therapy·Yuqing WangKen-ichiro Kosai
Apr 15, 2011·Trends in Endocrinology and Metabolism : TEM·Joseph S MarinoJennifer W Hill
May 3, 2008·Regulatory Peptides·Rubén NogueirasMatthias H Tschöp
Jan 12, 2007·Peptides·Satya P Kalra, Pushpa S Kalra
Dec 18, 2007·Journal of Neuroendocrinology·A M van den HoekH Pijl
Feb 18, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Urszula T IwaniecSatya P Kalra
Sep 12, 2006·Peptides·Stéphane BoghossianSatya P Kalra
Apr 7, 2015·The Journal of Nutritional Biochemistry·Maharshi BhaswantLindsay Brown
May 2, 2014·Neurobiology of Disease·Cecilia DavisMeredith Hawkins
Sep 23, 2016·Molecular Metabolism·Heather C DenrocheTimothy J Kieffer
Oct 27, 2016·Journal of Neuroendocrinology·S R Ladyman, D R Grattan
Dec 2, 2017·The Journal of Endocrinology·Kenneth A PhilbrickUrszula T Iwaniec
Jul 31, 2018·Endocrine Reviews·Karen D CorbinUNKNOWN Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON)
Oct 31, 2008·The Journal of Pharmacology and Experimental Therapeutics·Cornelia B LandersdorferWilliam J Jusko
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Biomarkers for Type 2 Diabetes

Biomarkers can help understand chronic diseases and assist in risk prediction for prevention and early detection of diseases. Here is the latest research on biomarkers in type 2 diabetes, a disease in which the body is unable to produce or properly use insulin.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.