Hyperleptinemia in obesity is the cause of central insulin resistance

While we still don’t know what directly causes type 2 diabetes, a new study could reveal how obesity and high levels of a fat-derived hormone called leptin can increase a person's risk of developing insulin resistance.

This is one of the reasons behind the link between obesity and type 2 diabetes as obesity changes the brain’s response to insulin.

Researchers from Monash University plan to block leptin action in the brains of obese mice with the hope of dramatically lowering glucose production by the liver.

The research led by Professor Michael Cowley, head of physiology, is supported by Diabetes Australia Research Trust.

“We have found that high leptin levels cause certain brain cells to stop responding to insulin,” says Cowley.

“Remarkably, these neurons normally inhibit hepatic glucose production (HGP).”

HGP is a key physiological process during which the liver produces glucose that becomes altered in people with diabetes as the liver begins to malfunction; making more glucose than necessary.

In people with type 2 diabetes, HGP can become dangerous as there’s not enough insulin production by the body to counteract it.

High levels of the fat-derived hormone leptin associated with obesity mean insulin can not act in the brain to reduce glucose production by the liver.

This in turn causes insulin secretion to work overtime to deal with the higher glucose levels in the blood stream, which contributes to insulin resistance and beta cell exhaustion which may cause type 2 diabetes.

By blocking those high levels of leptin in the brains of obese mice, Cowley and his team hope to significantly lower HGP by the liver.

“Increased HGP contributes significantly to beta cell exhaustion and the loss of insulin secretion in type 2 diabetes,” Cowley says.

“Hopefully we can learn more about how these neurons suppress glucose production in the liver, so that we can develop new therapies to reduce blood glucose.”

Diabetes Australia is the national body representing people affected by all types of diabetes and those at risk. Diabetes Australia is committed to reducing the impact of diabetes. We work in partnership with diabetes health professionals, researchers, and the community to minimise the impact of diabetes.