Stomach Hormone May Treat Diabetic Neuropathy

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SAN DIEGO—Ghrelin, a peptide produced in the stomach, given as an intravenous (IV) injection may help combat diabetic neuropathy, according to Japanese investigators.

The investigators presented data at the Endocrine Society's 92nd Annual Meeting showing that diabetes-related nerve damage of the feet and legs (polyneuropathy) improves after treatment with ghrelin.

Ghrelin increases food intake and increases growth hormone secretion. It also suppresses inflammation and oxidative stress and promotes cell survival and proliferation. Because of its diverse action, ghrelin may have many clinical applications; it also is being tested for the treatment of anorexia nervosa, diabetic gastroparesis, and cachexia. 

Ghrelin's main function is to transiently increase secretion of growth hormone. Patients with diabetes have suppressed growth hormone secretion, which is one of the causes of their metabolic imbalance.

“Ghrelin is a potential novel therapeutic approach for the treatment of polyneuropathy, an otherwise intractable disorder,” said researcher Masamitsu Nakazato, MD, PhD, Professor of Medicine at the University of Miyazaki in Miyazaki, Japan.

Dr. Nakazato and his colleagues first studied the effects of intraperitoneal administration of synthetic ghrelin in mice with chemically induced diabetes. They evaluated nerve injury using the nerve conduction velocities test, which measures the speed of electrical signals through the nerve in response to a mild electrical stimulation. A decreased velocity indicates nerve damage.  The investigators found that ghrelin improved reductions in motor and sensory nerve conduction velocities in the diabetic mice and normalized their temperature sensation.

They then tested IV ghrelin therapy in three men with type 2 diabetes who were not taking insulin. These men received gherlin therapy for two weeks after breakfast so that the ghrelin would not stimulate food intake. “After ghrelin treatment, all three patients had improved nerve conduction velocity of the lower limbs and improved symptoms of polyneuropathy,” said Dr. Nakazato, who presented the study findings.

The patients did not gain any weight or have any worsening of their blood sugar levels as a result of ghrelin therapy. Overall, it appeared that this treatment did not alter glucose metabolism or body weight. The agent was tested in healthy individuals as well as the three diabetic subjects.  Ghrelin therapy increased plasma growth hormone levels by 60 ng/mL in healthy subjects and 16 ng/mL in the diabetics 15 minutes after IV injection.

“We didn't find any side effects with ghrelin,” Dr. Nakazato said. “This may offer a new therapeutic paradigm for diabetes and diabetes complications.”

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