Knockout of TXNIP improves diabetes-associated hyperglycemia and hyperglucagonemia.
Anath Shalev, M.D.In groundbreaking diabetes research over the past two decades, Anath Shalev, M.D., has shown that the protein TXNIP regulates survival and function of beta cells, the pancreatic cells that produce the hormone insulin to lower levels of glucose in the blood. Downregulation or inhibition of TXNIP in beta cells protects against diabetes in mouse models, and a repurposed clinical drug that inhibits TXNIP shows promising results in people with recent-onset Type 1 diabetes.
Beta cells play a key role in the pathogenesis of both Type 1 and Type 2 diabetes. However, pancreatic islets also have alpha cells that produce the hormone glucagon, which acts to raise glucose blood levels. Together, insulin and glucagon keep blood glucose levels stable.
To further understand the role of TXNIP in pancreatic islet biology and glucose control, Shalev and colleagues at the University of Alabama at Birmingham now report the effect of knocking out TXNIP in alpha cells.
While not as dramatic as beta-cell TXNIP knockouts, the alpha-cell knockout improved diabetes-associated hyperglycemia and hyperglucagonemia in a mouse model of streptozotocin-induced diabetes. Hyperglycemia and hyperglucagonemia excess levels of glucose and glucagon in the blood are hallmarks of diabetes.
The alpha-cell knockouts, known as aTKO mice, had normal glucose homeostasis and no gross abnormalities when fed on regular chow food. However, when the aTKO mice were fed a high-fat diet for 30 weeks to create glucose intolerance, they had a reduced high-fat diet-induced glucose intolerance compared to control mice on the high-fat diet. Glucose intolerance is an impaired ability to respond to a surge of dietary glucose.
In the knockout mice, there was no change in the architecture of the aTKO islets and the alpha cell numbers were unchanged. Furthermore, the expression levels of the glucagon gene and key islet transcription factors showed no change. However, glucagon secretion was decreased more than twofold in the aTKO islets compared to controls.
Out of five proteins recently reported to be involved in alpha cell glucagon expression, only one, Grp78, had significantly changed expression in the aTKO islets. This protein was recently confirmed to interact with glucagon in secretory granules, and it acts as a molecular chaperone in the cells endoplasmic reticulum, the transportation system of the cell where proteins are produced.
Thus, it appears that downregulation of alpha cell TXNIP can inhibit alpha cell glucagon secretion, which in turn may help explain the improvement in hyperglucagonemia and hyperglycemia observed in diabetic aTKO mice.
Interestingly, we recently found that pharmacological inhibition of TXNIP with a small molecule inhibitor also resulted in decreased alpha cell glucagon secretion in vitro in alphaTC1-6 cells and in vivo in different diabetes mouse models, said Shalev, director of the UAB Comprehensive Diabetes Center and professor in the Department of Medicine Division of Endocrinology, Diabetes and Metabolism. These findings strongly support our current results using genetic TXNIP deletion and together suggest that alterations in TXNIP regulate alpha cell glucagon secretion.
Co-authors with Shalev on the paper, Alpha cell TXNIP deletion improves diabetes-associated hyperglycemia and hyperglucagonemia, published in the journal Endocrinology, are Brian Lu, Junqin Chen, Guanlan Xu, Truman B. Grayson, Gu Jing and SeongHo Jo, all members of the UAB Comprehensive Diabetes Center and the UAB Department of Medicine, Division of Endocrinology, Diabetes and Metabolism.
Support came from National Institutes of Health grants DK078752 and Human Islet Research Network DK120379.
At UAB, Shalev holds the Nancy R. and Eugene C. Gwaltney Family Endowed Chair in Juvenile Diabetes Research. Medicine is a department in the Marnix E. Heersink School of Medicine.
Go here to read the rest:
Diabetes: TXNIP involved in increased secretion of glucagon from pancreatic alpha cells - University of Alabama at Birmingham
- Virginia to offer diabetes-prevention classes - Essentia Health - March 1st, 2024
- Type 2 Diabetes: Red Light Therapy May Help Lower Blood Sugar - Healthline - March 1st, 2024
- Ultra-processed foods linked to over 30 health issues, from diabetes to heart trouble to cancer, research finds - CBS News - March 1st, 2024
- Mayo Clinic Minute: Expanding the living kidney donor pool to those with Type 2 diabetes - Mayo Clinic - March 1st, 2024
- Sugar tax shows sweet results in cutting obesity and diabetes rates - News-Medical.Net - March 1st, 2024
- What's the Connection Between Diabetes and Oral Health? - Medscape - March 1st, 2024
- ATTD 2024: Previewing the Latest on AID Systems, CGMs, and Diabetes Medications - diaTribe Foundation - March 1st, 2024
- What I Wish I Had Known When I Was Diagnosed with Type 2 Diabetes - EatingWell - March 1st, 2024
- Ultraprocessed foods linked to heart disease, diabetes, mental disorders and early death, study finds - CNN - March 1st, 2024
- Type 2 diabetes: Red light therapy could help lower blood sugar levels - Medical News Today - March 1st, 2024
- Unraveling the Link Between Type 2 Diabetes and Lower Back Pain: A New Frontier in Medical Research - Medriva - March 1st, 2024
- Scientists from 18 countries join forces to put end to 'pervasive, global problem' of diabetes stigma and discrimination - Medical Xpress - March 1st, 2024
- Bariatric surgery more effective than medical and lifestyle interventions for diabetes control and remission: Study - Medical Xpress - March 1st, 2024
- Unveiling Growth Prospects in the Type 2 Diabetes Industry: Major Drivers And Lucrative Segments As Per The ... - GlobeNewswire - March 1st, 2024
- Insulin-inhibitory receptor research offers hope for type 2 diabetes therapy - Medical Xpress - March 1st, 2024
- Over 4,800 persons with suspected symptoms of diabetes, hypertension identified during screening - The Hindu - March 1st, 2024
- Free cooking classes to be held in March to prevent Type 2 diabetes in Delco - The Delaware County Daily Times - March 1st, 2024
- Noblesville basketball's Aaron Fine hopes to inspire others with diabetes - IndyStar - March 1st, 2024
- One secret to preventing dementia, diabetes, and heart disease may lie in your oral health habits. Here's the dental ... - Fortune - March 1st, 2024
- Diabetes blood sugar reduction through new technology - The Jerusalem Post - March 1st, 2024
- More Funding to Reduce Costs, Improve Diabetes Care - Government of Nova Scotia - March 1st, 2024
- Many diagnosed with Type 2 diabetes may have a different form of the disease - NBC News - January 14th, 2024
- AI and the safe travel lane of diabetes care - Central Michigan University - January 14th, 2024
- Independent association of history of diabetic foot with all-cause mortality in patients with type 2 diabetes: the Renal ... - Cardiovascular... - January 14th, 2024
- Food an Effective Medicine in Diabetes? - Medscape - January 14th, 2024
- New insight into the pathogenesis of human diabetes - VA News - Veterans Affairs (.gov) - January 14th, 2024
- Controversy surrounding diabetes drug, Ozempic, being used tor weight loss - LiveNOW from FOX - January 14th, 2024
- Why are drugs that help battle obesity and diabetes so hard to get? - The Seattle Times - January 14th, 2024
- Semaglutide linked to lower suicidal ideation risk than other obesity, diabetes drugs - Healio - January 14th, 2024
- 5 "Bad" Carbs You Should Be Eating When You Have Diabetes, According to a Dietitian - EatingWell - January 14th, 2024
- 5 Breakfast Mistakes to Avoid If You Have Diabetes - EatingWell - January 14th, 2024
- Why don't fruit bats get diabetes? New understanding of how they've adapted to a high-sugar diet could lead to ... - The Conversation - January 14th, 2024
- OU professor discovers possible link between breast cancer drugs and Type 2 diabetes - KOCO Oklahoma City - January 14th, 2024
- Regional Union Selects Dario's Cardiometabolic Solution for Diabetes, Hypertension, Weight Management and GLP-1 ... - PR Newswire - January 14th, 2024
- Loneliness Associated With Greater Burden of Care Among Caregivers of Children With Type 1 Diabetes - Drug Topics - January 14th, 2024
- Is Yogurt Good For Diabetes Or Not? A Review By Nutrition Professionals - MSN - January 14th, 2024
- Health Insurance Coverage and Costs for Type 1 Diabetes Screening - Beyond Type 1 - January 14th, 2024
- MCH to open free diabetes clinic thanks to $500,000 received from the City of Odessa - NewsWest9.com - January 14th, 2024
- Smart pens and insulin pump therapy for people with Type 2 diabetes - Omnia Health Insights - January 14th, 2024
- Tandem Diabetes Care's t:slim X2 Insulin Pump is the First Automated Insulin Delivery System to Integrate with ... - Yahoo Finance - January 14th, 2024
- Why fruit bats can eat tons of sugar without getting diabetes - Popular Science - January 14th, 2024
- Effect of Self-Care Activities and Behaviors on Glycemic Control in Patients With Diabetes at a Tertiary Care Hospital in ... - Cureus - January 14th, 2024
- This Is the Absolute Best Way To Stay Hydrated if You Have Diabetes - Northwest Georgia News - January 14th, 2024
- Artificial sweeteners dont aid weight loss, may increase diabetes, heart disease risk, says WHO - ThePrint - May 17th, 2023
- Diabetes: What It Is, Causes, Symptoms, Treatment & Types - April 23rd, 2023
- Medically supervised weight loss approach helps patients reduce risks of diabetes, heart disease and stroke - ABC4.com - April 23rd, 2023
- Dear Annie: Im worried about my sisters use of diabetes injections to drop a few pounds - OregonLive - February 6th, 2023
- Diabetes Drug Mounjaro Expected To Be Approved For Weight Loss Soon: What To Know And How It Compares To Similar Drugs - Forbes - February 6th, 2023
- Alcohol: Some People Have Higher Risk Of Heart Attack, Diabetes And Stroke More Than Binge Drinkers Signs Youre At Risk - Revyuh - February 6th, 2023
- Still Drinking Green Tea? Doctor Reveals A Healthier Drink With Proven Benefits For Diabetes, Aging, Oxidative Stress, And Cancer - Revyuh - January 4th, 2023
- How Cinnamon Lowers Blood Sugar and Fights Diabetes - Healthline - December 27th, 2022
- Diabetic Foot Ulcers: Causes and Treatments - Healthline - December 27th, 2022
- Diabetes: Are jaggery and honey healthier alternatives to sugar? Experts help you understand - Times of India - December 2nd, 2022
- Diabetes | Sutter Health - November 24th, 2022
- Effect of diet on type 2 diabetes mellitus: A review - PMC - November 24th, 2022
- Efficacy of Berberine in Patients with Type 2 Diabetes - PMC - November 24th, 2022
- First Drug to Delay Type 1 Diabetes Approved by FDA - Smithsonian Magazine - November 24th, 2022
- Learn how to prevent and manage diabetes - Lincoln Journal Star - October 29th, 2022
- Resilience may improve health among older adults with type 2 diabetes - Medical News Today - October 13th, 2022
- Years of Diabetes Could Speed Onset of Menopause | Health | derbyinformer.com - The Derby Informer - October 13th, 2022
- Insulin Use May Predict the Development of Diabetic Retinopathy - MD Magazine - October 13th, 2022
- The Most Crucial Eating Habit To Prevent Diabetes - Eat This, Not That - October 13th, 2022
- 2 Northeast Ohio teens born with type 1 diabetes deal with social anxieties of their condition at school - WKYC.com - October 13th, 2022
- University Hospitals nationally recognized for efforts to reduce uncontrolled blood pressure; address relationship between diabetes, heart disease,... - October 13th, 2022
- 5 Analysts Have This to Say About Tandem Diabetes Care - Tandem Diabetes Care (NASDAQ:TNDM) - Benzinga - October 13th, 2022
- Living with diabetes: Nutrition, exercise, routines, and more - Medical News Today - October 4th, 2022
- Cleveland Clinic - October 4th, 2022
- Researchers study long-term effectiveness of diabetes drugs - GW Hatchet - October 4th, 2022
- Once-weekly insulin icodec demonstrates superior reduction in HbA1c in combination with a dosing guide app versus once-daily basal insulin in people... - October 4th, 2022
- THE DIABETES LINK LAUNCHES TO HELP YOUNG ADULTS THRIVE WHILE LIVING WITH THE DISEASE - PR Newswire - October 4th, 2022
- Why people with diabetes have more UTIs and how to prevent infections - Medical News Today - October 4th, 2022
- Dealing With Type 1 Diabetes - Nick Jonas Behind New Men's Mental Health Initiative - Men's Health - October 4th, 2022
- Bionic pancreas improves type 1 diabetes management compared to standard insulin delivery methods - National Institutes of Health (.gov) - October 4th, 2022
- NOACs or Warfarin in Atrial Fibrillation With Diabetes - DocWire News - October 4th, 2022
- Why Type 1 Diabetes Is Tougher on Girls Than Boys - Healthline - October 4th, 2022
- Improve Diagnosis of Type of Heart Failure Common in Diabetes - Medscape - October 4th, 2022
- Insights on the Next Generation Diabetes Therapy and Drug Delivery Global Market to 2030 - Rising Incidences of Diabetes Globally and Increase in the... - October 4th, 2022
- Peanut Butter and Diabetes: Can They Work Together? - Taste of Home - October 4th, 2022
- Prevalence of Microalbuminuria and Cardiovascular Risk Factors in Patients With Diabetes Mellitus Type-II in Al-Khobar, Kingdom of Saudi Arabia -... - October 4th, 2022
- Do Well, Be Well with Diabetes program starts Oct. 6 in Waco - AgriLife Today - September 25th, 2022