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. Author manuscript; available in PMC: 2014 May 13.
Published in final edited form as: Nat Rev Drug Discov. 2012 Sep;11(9):692–708. doi: 10.1038/nrd3757

Figure 4. CNS Neuronal Mediators, Efferent Pathways, and Peripheral Mechanisms Underlying the Anti-Diabetic Actions of Leptin.

Figure 4

A. Schematic model of central neuronal pathways and efferent processes whereby leptin exerts its anti-diabetic actions in insulin-resistance and obese mice (e.g. genetically modified db/db animals). ARH POMC-expressing neurons are currently the best candidates responsible for mediating the improved glucose control by leptin in the db/db Type 2 diabetic rodent models, although AgRP-expressing neurons and other hypothalamic and extra-hypothalamic neurons are also likely to play important roles. These neurons act via axonal projections on downstream neurocircuits (e.g. the melanocortin system) to engage efferent pathways. This may include regulation of sympathetic (SNS) and parasympathetic (PNS) branches of the autonomic nervous system, ultimately affecting muscle glucose uptake, pancreatic glucagon production and/or hepatic glucose production. B. ARH leptin-target neurons, including POMC neurons, produce and secrete a number of different molecules from axon terminals, including the POMC-polypeptide-derived neuropeptides; alpha-melanocortin stimulating hormone (α-MSH) and β-Endorphin. Cocaine and amphetamine-regulated transcript (Cart) and Nesfatin-1 is also co-expressed with POMC peptides. Finally, these ARH neurons are heterogeneous with regard to neurotransmitter phenotype; different subpopulations produce glutamate, GABA and acetylcholine (ACh). Combined, these neurotransmitters and neuropeptides are the candidate effector-molecules to mediate glycemic control by leptin in the db/db model.