Hyperinsulinemia precedes insulin resistance in mice lacking pancreatic beta-cell leptin signaling

Endocrinology
Sarah L GrayT J Kieffer

Abstract

The adipocyte hormone leptin acts centrally and peripherally to regulate body weight and glucose homeostasis. The pancreatic beta-cell has been shown to be a key peripheral target of leptin, with leptin suppressing insulin synthesis and secretion from beta-cells both in vitro and in vivo. Mice with disrupted leptin signaling in beta-cells (lepr(flox/flox) RIPcre tg+ mice) display hyperinsulinemia, insulin resistance, glucose intolerance, obesity, and reduced fasting blood glucose. We hypothesized that hyperinsulinemia precedes the development of insulin resistance and increased adiposity in these mice with a defective adipoinsular axis. To determine the primary defect after impaired beta-cell leptin signaling, we treated lepr(flox/flox) RIPcre tg+ mice with the insulin sensitizer metformin or the insulin-lowering agent diazoxide with the rationale that pharmacological improvement of the primary defect would alleviate the secondary symptoms. We show that improving insulin sensitivity with metformin does not normalize hyperinsulinemia, whereas lowering insulin levels with diazoxide improves insulin sensitivity. Taken together, these results suggest that hyperinsulinemia precedes insulin resistance in beta-cell leptin receptor-def...Continue Reading

References

Jun 1, 1992·Diabetes Care·C J Bailey
Dec 1, 1991·The Journal of Clinical Endocrinology and Metabolism·R A DeFronzoD C Simonson
Jan 1, 1985·The Journal of Clinical Endocrinology and Metabolism·M ChenD Porte
Aug 31, 1995·The New England Journal of Medicine·M StumvollJ E Gerich
Jul 28, 1995·Science·M A PelleymounterF Collins
Aug 1, 1993·Endocrinology·R AlemzadehJ Maturo
Mar 1, 1996·Metabolism: Clinical and Experimental·R AlemzadehP Pitukcheewanont
Jul 16, 1996·Biochemical and Biophysical Research Communications·T J KiefferJ F Habener
Feb 12, 1998·The Journal of Clinical Investigation·R N KulkarniS R Bloom
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·J SeufertJ F Habener
Jan 25, 2000·American Journal of Physiology. Endocrinology and Metabolism·T J Kieffer, J F Habener
Mar 4, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M StandridgeN Moustaid-Moussa
Apr 6, 2002·American Journal of Physiology. Endocrinology and Metabolism·Chia-Yu LinB Douglas White
Dec 10, 2002·Annual Review of Physiology·Roger H Unger
Apr 23, 2003·Molecular and Cellular Endocrinology·P MaroniR Piccoletti
Jan 30, 2004·Recent Progress in Hormone Research·Christian Bjørbaek, Barbara B Kahn
Aug 21, 2004·Endocrinology·Ramin Alemzadeh, Kathryn M Tushaus
Jul 21, 2005·International Journal of Obesity : Journal of the International Association for the Study of Obesity·R B Ceddia
Sep 15, 2005·International Journal of Obesity : Journal of the International Association for the Study of Obesity·R H LustigJ Hohneker
Oct 29, 2005·The Journal of Comparative Neurology·Joel K ElmquistBradford B Lowell
Feb 8, 2006·Journal of Molecular Endocrinology·N T LamT J Kieffer
Jul 11, 2006·The Journal of Clinical Investigation·Masato Kasuga
Jul 11, 2006·The Journal of Clinical Investigation·Marc Prentki, Christopher J Nolan
Aug 18, 2006·Current Medical Research and Opinion·Bart Staels
Aug 26, 2006·Nature Clinical Practice. Endocrinology & Metabolism·Robert H Lustig
Oct 3, 2007·The Journal of Clinical Investigation·Kevin D Niswender, Mark A Magnuson
Oct 3, 2007·The Journal of Clinical Investigation·Tomoaki MoriokaRohit N Kulkarni
Sep 18, 2008·International Journal of Obesity : Journal of the International Association for the Study of Obesity·D G Hardie
Dec 27, 2008·Biochimica Et Biophysica Acta·Andrea Zsombok, Bret N Smith
Jan 24, 2009·Nature Clinical Practice. Endocrinology & Metabolism·Ritika R KapoorKhalid Hussain

❮ Previous
Next ❯

Citations

Mar 9, 2013·Frontiers of Medicine·Jianping Ye
May 19, 2011·American Journal of Physiology. Endocrinology and Metabolism·Jie NingWenhong Cao
Nov 30, 2010·International Journal of Endocrinology·Chunjiong WangJichun Yang
Mar 27, 2012·Journal of Molecular Endocrinology·Laura MarroquíIvan Quesada
Jun 2, 2014·Journal of Endocrinological Investigation·Shengqiang ShuGaohua Wang
Mar 12, 2013·Endocrine Reviews·Hyun-Seuk MoonChristos S Mantzoros
Oct 9, 2015·Molecular Nutrition & Food Research·Celina Carvalho BorgesMarcia Barbosa Aguila
Mar 28, 2012·Journal of Diabetes Investigation·Heather C DenrocheTimothy J Kieffer
May 21, 2013·Biochimica Et Biophysica Acta·Ruth B S Harris
Jul 3, 2015·Molecular Metabolism·David J PedersenMichael P Czech
Feb 1, 2015·Molecular Aspects of Medicine·Leslie S SatinArthur S Sherman
Jun 3, 2011·Metabolism: Clinical and Experimental·Yong-ho LeeEun Seok Kang
Dec 12, 2012·Cell Metabolism·Arya E MehranJames D Johnson
Jun 25, 2016·The Journal of Endocrinology·Sujith RajanAnil N Gaikwad
Aug 16, 2016·Molecular and Cellular Endocrinology·Muheeb BegAnil N Gaikwad
Jan 26, 2017·Neuroendocrinology·Weiyi ChenMichael A Cowley
Jan 6, 2017·The Journal of Endocrinology·Nicole M TemplemanJames D Johnson
Jun 4, 2019·International Journal of Molecular Sciences·Veronica Cochrane, Show-Ling Shyng
Nov 11, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Melissa M PageJames D Johnson
May 4, 2017·Current Obesity Reports·Karel A Erion, Barbara E Corkey
Nov 21, 2019·Journal of Alzheimer's Disease : JAD·Vijay HegdeP Hemachandra Reddy
Jun 21, 2020·Current Problems in Cardiology·Abdul WahabHani Jneid
Nov 8, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Francielle Graus-Nunes, Vanessa Souza-Mello
Feb 26, 2021·Cellular Signalling·Dominik WiggerBurkhard Kleuser
May 22, 2020·Journal of Inorganic Biochemistry·Samuel Treviño, Alfonso Diaz

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.