Alpha melanocyte stimulatory hormone and improvements in glucose tolerance in humans: Role of enhanced skeletal muscle glucose uptake and utilisation

Patients with diabetes show significant impairements in the control of blood levels of nutrients such as sugars and fats after eating. This causes excessive levels of nutrient to circulate (e.g. high blood sugar-hyperglycaemia) and over time this phenomenon can injure cells and tissues of the body resulting in complications such as heart attacks, blindness and kidney failure.

Patients with Type 1 Diabetes and advanced Type 2 diabetes require life-long treatment with the hormone insulin which corrects a deficiency in the production and action of insulin their own bodies. While insulin therapy is effective it can come with significant side-effects especially when used intensively. Dangerously low levels of blood sugar (hypoglycaemia) and excessive weight gain can both occur as a result of intensive insulin therapy and can detract from the benefits of a reduction in hyperglycaemia.

Some drugs exist that can theoretically help insulin to work more effectively at lower doses exist and are in clinical use but these can also be associated with undesirable effects such as weight gain. We have discovered that a hormone from the pituitary gland in the brain called alpha melanocyte stimulatory hormone (alpha-MSH) plays a role in normal physiological response to eating by helping to reduce blood glucose. Furthermore we have demonstrated that if we provide alpha-MSH as an infusion in mice and sheep it can improve blood sugar levels.

We now wish to characterise these effects in humans, specifically looking at whether the benefits depend upon an increased capacity for skeletal muscle to tissue to extract glucose and use circulating glucose in the period after eating.

The work proposed in the current application will prove critical insight into whether alpha-MSH improves bood sugar control in humans and whether it thus holds potential to be developed as a new drug for the treatment of diabetes.


Award Date
30 June 2017
Award Value
€361,679
Principal Investigator
Professor Neil Docherty
Host Institution
University College Dublin
Scheme
Investigator Led Projects