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Final Report Summary - LEPTINT1DM (Unraveling the mechanism underlying the anti-diabetic action of leptin)

Summary description of the project objectives:
The main objective of the project is to determine whether leptin action on POMC neurons is required and/or sufficient for leptin’s anti-type 1 diabetic action in mice.

Description of the work:
To determine whether leptin action on POMC neurons is required and/or sufficient for leptin’s anti-type 1 diabetic action in mice, we generated mice lacking or expressing leptin receptors only in POMC neurons. Pancreatic insulin-producing beta-cells were destroyed rendering these mutants type 1 diabetic. Intracranial administration of leptin was then achieved and clinical symptoms of type 1 diabetes monitored over time.

Description of the main results achieved:
The hyperglycemia-lowering action of leptin administration was partially blunted in type 1 diabetic mice lacking leptin receptors only in POMC neurons. On the other hand, the hyperglycemia-lowering action of leptin administration was completely abolished in type 1 diabetic mice expressing leptin receptors only in POMC neurons.

Expected final results and their potential impact and use (including the socio-economic impact and the wider societal implications of the project so far):

Leptin receptors on POMC neurons play a minor role for leptin’s anti-type 1 diabetic action. Thus leptin action on other non-POMC neurons exerts a major role for leptin’s anti-type 1 diabetic effect. Understanding the neuronal and molecular mechanisms underlying leptin action in type 1 diabetes will identify new molecular targets for counteracting the metabolic dysfunctions caused by insulin deficiency. Hence, these studies have the potential to significantly improve diabetes care.

Reported by

UNIVERSITE DE GENEVE
Switzerland

Subjects

Life Sciences
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