Abstract
Ample animal studies demonstrate that neuropeptides NPY and α-MSH expressed in Arcuate Nucleus and Nucleus of the Tractus Solitarius, modulate glucose homeostasis and food intake. In contrast is the absence of data validating these observations for human disease. Here we compare the post mortem immunoreactivity of the metabolic neuropeptides NPY, αMSH and VGF in the infundibular nucleus, and brainstem of 11 type-2 diabetic and 11 non-diabetic individuals. α-MSH, NPY and tyrosine hydroxylase in human brain are localized in the same areas as in rodent brain. The similar distribution of NPY, α-MSH and VGF indicated that these neurons in the human brain may share similar functionality as in the rodent brain. The number of NPY and VGF immuno positive cells was increased in the infundibular nucleus of diabetic subjects in comparison to non-diabetic controls. In contrast, NPY and VGF were down regulated in the Nucleus of the Tractus Solitarius of diabetic patients. These results suggest an activation of NPY producing neurons in the arcuate nucleus, which, according to animal experimental studies, is related to a catabolic state and might be the basis for increased hepatic glucose production in type-2 diabetes.
Highlights
Animal studies have shown that the levels of circulating insulin and glucose are monitored in the Arcuate nucleus (ARC) of the hypothalamus and the caudal brainstem
POMC is the precursor of several neuropeptides of which alpha-melanocyte stimulating hormone (a-MSH) is the cleavage product that mediates the effects on metabolism [9]
We investigated the expression of Neuropeptide Y (NPY), a-MSH and VGF in the post mortem brain of type-2 diabetic individuals which was compared with their expression in brains obtained from age and sex matched non-diabetic patients
Summary
Animal studies have shown that the levels of circulating insulin and glucose are monitored in the Arcuate nucleus (ARC) of the hypothalamus and the caudal brainstem. Changing concentrations of insulin and glucose modify the activity of several neuronal populations within these areas These nutrient/hormone sensitive neurons project to pre-autonomic neurons located in the hypothalamus and brainstem and modulate the autonomic output to liver and pancreas. In both areas, neurons were identified that are either activated or inhibited by changes in glucose availability [1,2,3,4]. VGF is a neuropeptide precursor co-expressed in NPY and POMC neurons of the rat arcuate nucleus. The ablation of the VGF gene produces a hyper phagic and hyper metabolic phenotype, and results in increased NPY and diminished POMC expression; typical of prolonged fasting [10]
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