• UCLA Health
  • myUCLAhealth
  • School of Medicine
U Magazine

U Magazine

U Magazine
  • Home
  • Current Issue
  • Centennial Campaign for UCLA Issue
  • Browse U Magazine
  • Letters to the Editor
  • Subscribe
  • Contact
  • UCLA Health
  • myUCLAhealth
  • School of Medicine

U Magazine

Browse U Magazine

  1. Home
  2. Browse U Magazine
Share this
The Cutting Edge

Can a “Battery Leak” Trigger the Onset of Type 2 Diabetes?

Could a leaky “battery” within our cells be at the core of the mechanism that sets off type 2 diabetes? New research by UCLA scientists may have opened a window to the answer.

A central question in diabetes research is why cells of the pancreas, known as beta cells, initially over-secrete insulin. The prevailing theory was that the body may be in the process of becoming “deaf” to insulin, so beta cells secrete more to compensate. But isolated beta cells still over-secrete insulin, which exposes a gap in that theory.

In the new study, researchers set out to understand what other mechanism beyond insulin resistance (that is, the body becoming “deaf” to insulin) and high glucose levels might explain why diabetes develops. The scientists found that a pathway independent of glucose, but sensitive to fatty acids, appears to drive insulin secretion in the early stages of diabetes.

The teams found that in beta cells from obese, pre-diabetic mice, a protein known as Cyclophilin D, or CypD, induced a phenomenon known as “proton leak,” and that this leak promoted insulin secretion in the absence of elevated glucose. The mechanism was dependent on fatty acids, which are normally incapable of stimulating insulin secretion in healthy animals.

Orian Shirihai, MD, PhD

Orian Shirihai, MD, PhD

“Beta cells are a remarkable sensor of glucose. They take the energy from the nutrients and store it in mitochondria, which are like miniature batteries,” explains Orian Shirihai, MD, PhD, professor of endocrinology and pharmacology. “Once the voltage in these batteries goes high, a unique combination of signals is transmitted to the cell membrane, leading to post-meal insulin secretion. For years, it has been known that beta cells from pre-diabetic humans and animals are very inefficient in delivering the energy from nutrients to secretion. The reason was attributed to a constant leak in their batteries, causing them to constantly lose energy.”

Once the team determined that the levels of leak closely predict the over-secretion of insulin, they decided to test what had not been previously considered: Perhaps in the pre-diabetic animal, it is the battery leak itself that produces an abnormal signal for secretion, even in the absence of elevated glucose. “Until that day,” Dr. Shirihai says, “we only considered a leak as a mechanism that will exhaust beta cells and impair their ability to respond to glucose. But we never tested the effect of such a leak in the absence of glucose. We were in for a big surprise that would require a significant shift in our thinking.”

The research further determined that obese mice who lacked the gene for CypD did not secrete excess insulin. The team confirmed the same process was taking place in isolated human pancreas cells. The results suggest new ways to prevent the development of insulin resistance and to treat diabetes, including halting its progression by blocking the proton leak in the beta cell.

— Alice Walton

 

“Mitochondrial Proton Leak Regulated by Cyclophilin D Elevates Insulin Secretion in Islets at Non-Stimulatory Glucose Levels,” Diabetes, November 2019


Previous
Targeted Therapy Drug Extends Lives of Women with Aggressive Breast Cancer
Next
Molecular Changes in Cells of Eye’s Lens Predict Future Cataracts


YOU ARE VIEWING

Winter 2020

Winter 2020
Printable PDF
IN THIS ISSUE
  • Lessons from Sherm
  • Father’s X Chromosome May Yield Clues to Higher Rates of Autoimmune Disease in Women
  • Researchers Create Accurate Model of Organ Scarring
  • Biomarker Predicts Which Heart-failure Patients at Higher Risk of Death within One-to-three Years
  • Targeted Therapy Drug Extends Lives of Women with Aggressive Breast Cancer
  • Can a “Battery Leak” Trigger the Onset of Type 2 Diabetes?
  • Molecular Changes in Cells of Eye’s Lens Predict Future Cataracts
  • UCLA Addresses Increasing Demand with New Master’s in Genetic Counseling
  • Truth Seeker
  • Sherm
  • Repairing and Reversing Damage Caused by Huntington’s Disease
  • Cells’ Mitochondria Work Much Like Tesla Battery Packs
  • The Who and Friends Rock Private Show for UCLA Health and Teen Cancer America
  • A Confounding Case
  • Body Image Concerns Are Universal
  • “We Do Better with Diversity”
  • Annual UCLA Health System Board Meeting Turns Its Focus to Cardiac Care
  • UCLA Operation Mend Cheered on at New York City Veterans Day Parade
  • A Decade in Review: 7 Exciting Health Care Breakthroughs
  • MRI May Help Doctors Differentiate Causes of Memory Loss
  • On the Road to Health Care Equality
  • Learning To Listen
  • Photo Synthesis
  • Awards & Honors
  • In Memoriam
  • David Geffen Adds $46 Million to Landmark Medical Scholarships Program
  • Nearly 2,000 Guests Attend Party on the Pier for UCLA Mattel Children’s Hospital
  • Golden Visionary Ball Raises More than $1 Million for UCLA Neurosurgery
  • Dr. Hans Gritsch Named Inaugural Chair in Kidney Transplantation
  • Nonprofit Heart of the Brain Fuels the Fight against Brain Cancer
  • UCLA Supporters Raise Money for Duchenne Muscular Dystrophy
  • Dancing for NED Fundraiser Fights Ovarian Cancer
  • Gifts
  • In Memoriam
Like Us on Facebook Follow Us on Twitter Subscribe to Our Videos on YouTube Follow us on Instagram Connect with Us on LinkedIn Follow us on Pinterest
UCLA Health hospitals ranked best hospitals by U.S. News & World Report
  • UCLA Health
  • Find a Doctor
  • School of Medicine
  • School of Nursing
  • UCLA Campus
  • Directory
  • Newsroom
  • Subscribe
  • Patient Stories
  • Giving
  • Careers
  • Volunteer
  • International Services
  • Privacy Practices
  • Nondiscrimination
  • Billing
  • Health Plans
  • Emergency
  • Report Broken Links
  • Terms of Use
  • 1-310-825-2631
  • Maps & Directions
  • Contact Us
  • Your Feedback
  • Report Misconduct
  • Get Social
  • Sitemap
Like Us on Facebook Follow Us on Twitter Subscribe to Our Videos on YouTube Follow us on Instagram Connect with Us on LinkedIn Follow us on Pinterest

Sign in to myUCLAhealth

Learn more about myUCLAhealth