Metabolic HealthAging Drives Excess Glucagon and Raises Diabetes Risk Even Before Insulin Resistance Appears
A new study in Aging Cell reveals that aging directly disrupts pancreatic alpha-cell biology, causing elevated fasting glucagon levels (hyperglucagonemia) even before insulin resistance develops. Using aged mice and data from the CORDIOPREV clinical study, researchers found that older animals had increased alpha-cell mass, higher glucagon content, impaired suppression of glucagon secretion at high glucose, and endoplasmic reticulum stress within alpha-cells. Islet architecture was also remodeled, with alpha-cells redistributing away from their normal peripheral position. In humans, older adults with insulin resistance showed hyperglucagonemia, and higher plasma glucagon was linked to a significantly increased risk of developing type 2 diabetes over time. The findings reframe alpha-cell dysfunction as a key, underappreciated contributor to age-associated metabolic disease.
