Disruption in the leptin-NPY link underlies the pandemic of diabetes and metabolic syndrome: new therapeutic approaches.

Nutrition
S P Kalra

Abstract

Multidisciplinary research from my and my colleagues' laboratory has shown that disruption at various levels of leptin signaling to the interactive hypothalamic network of neuropeptide Y (NPY) and cohorts contributes to the antecedent pathophysiologic sequelae of the disease cluster of the metabolic syndrome. Disruptions in NPY signaling due to high or low abundance of NPY and cognate receptors dysregulate the homeostatic milieu to promote hyperinsulinemia, hyperglycemia, fat accrual, and overt diabetes. Hyperleptinemia induced by consumption of energy-rich diets inhibits leptin transport across the blood-brain barrier and thereby produces leptin insufficiency in the hypothalamus. Sustained leptin insufficiency results in loss of hypothalamic restraint on pancreatic insulin secretion and diminished glucose metabolism and energy expenditure. This chain of events culminates in hyperinsulinemia, hyperglycemia, and diabetes. Our recent studies have shown that increasing the supply of leptin centrally by gene therapy reinstates the restraint on hypothalamic NPY signaling and ameliorates diabetes and the attendant disease cluster of the metabolic syndrome. Thus, newer therapies that would enhance leptin transport across the blood-bra...Continue Reading

References

Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·S P KalraP S Kalra
Apr 6, 2001·Diabetes·M TschöpM L Heiman
Oct 17, 2001·The Journal of Clinical Investigation·P CohenJ M Friedman
Feb 13, 2003·Drugs of Today·Pushpa S Kalra, Satya P Kalra
Aug 23, 2003·Endocrinology·Stephen O'RahillyBenjamin G Challis
Jun 8, 2004·The Journal of Clinical Endocrinology and Metabolism·Scott M Grundy
Feb 3, 2005·The Journal of Endocrinology·Katie WynneSteve Bloom
Jul 27, 2005·Peptides·Stéphane BoghossianSatya P Kalra
Sep 12, 2006·Peptides·Stéphane BoghossianSatya P Kalra
Jan 12, 2007·Peptides·Satya P Kalra, Pushpa S Kalra
Jan 16, 2007·Peptides·Michael G DubePushpa S Kalra

❮ Previous
Next ❯

Citations

Dec 5, 2012·Health Promotion International·Emely De VetMaarten Wesselman
Jan 26, 2011·Expert Opinion on Therapeutic Targets·Niki KatsikiDimitrios Karamitsos
Aug 10, 2010·Expert Opinion on Biological Therapy·Yuqing WangKen-ichiro Kosai
Apr 12, 2016·Clinics in Liver Disease·Pushpjeet Kanwar, Kris V Kowdley
Aug 30, 2008·Nutrition·Michael M MeguidFrank A Middleton
Aug 30, 2008·Nutrition·Sergueï O FetissovPierre Déchelotte
Aug 12, 2009·Neurobiology of Disease·Alan M Palmer
Jun 7, 2011·Peptides·Ana R DâmasoMarco Túlio de Mello
Jul 8, 2010·Journal of Emergencies, Trauma, and Shock·Luigi BerettaMarco Braga
Dec 19, 2017·Global Heart·Jeffrey I MechanickW Timothy Garvey
Aug 19, 2009·Current Opinion in Endocrinology, Diabetes, and Obesity

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Atrophic Gastritis

Atrophic Gastritis is a process where gastric glandular cells are lost and replaced with firbous tissues, as a result of chronic inflammation. Learn more about Atrophic Gastritis here.

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.

Cardiovascular Inflammation

Inflammation plays a significant role in the development of cardiovascular diseases, an understanding of these endogenous processes is critical for evaluating the risks and potential treatment strategies. Discover the latest research on cardiovascular inflammation here.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

CV Disorders & Type 2 Diabetes

This feed focuses on the association of cardiovascular diseases in patients with type 2 diabetes.

Blood Brain Barrier & Cytokines

Some cytokines are able to cross the blood brain barrier through transport systems and enter the cerebrospinal fluid and interstitial fluid spaces. Here is the latest research on cytokines crossing the blood brain barrier and how this can affect tissues within the CNS.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.