NPY and VGF Immunoreactivity Increased in the Arcuate Nucleus, but Decreased in the Nucleus of the Tractus Solitarius, of Type-II Diabetic Patients

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.

The impact of antidiabetic treatment on human hypothalamic infundibular neurons and microglia

“…However, studies in the hypothalamus of human T2DM patients are scarce, and the few studies performed to date show conflicting results. One study showed an increase of NPY-ir neurons without changes in the POMC-ir neurons ( 6 ), whereas a different study showed no effect on NPY-ir neurons, but a decrease of POMC-ir neurons ( 3 ). Both studies used postmortem brain tissue and matched the T2DM and CTRL subjects for sex, age, and PMD.…”

“…Numerous studies have focused on the hypothalamic infundibular nucleus (IFN, equivalent to the arcuate nucleus in rodents), which contains 2 key neuronal populations regulating energy homeostasis, proopiomelanocortin-expressing (POMC-expressing) and neuropeptide Y (NPY)/agouti-related protein–expressing (AgRP-expressing) neurons. Diet-induced obesity and T2DM have been associated with a disturbed balance between the anorexigenic POMC ( 3 , 4 ) and the orexigenic NPY/AgRP neurons ( 5 , 6 ).…”

Suprachiasmatic Nucleus Interaction with the Arcuate Nucleus; Essential for Organizing Physiological Rhythms

“…Indeed, the SCN receives a myriad of nonphotic input, arousal (Antle and Mistlberger, 2000), feeding behavior (Abe et al, 1989; Mendoza, 2007), locomotor activity (Edgar et al, 1991; Marchant and Mistlberger, 1995), immune function (O'Callaghan et al, 2012; Guerrero-Vargas et al, 2014), blood pressure (Peters et al, 1994; Buijs et al, 2014), and melatonin (Armstrong, 1989; Pitrosky et al, 1999), which are all able to adjust and synchronize the SCN. The SCN is capable of receiving this feedback through its large array of reciprocal neuronal connections with, e.g., the arcuate nucleus (ARC; Saeb-Parsy et al, 2000; Yi et al, 2006), intergeniculate leaflet (IGL; Janik and Mrosovsky, 1994; Saderi et al, 2012), nucleus tractus solitarius (Buijs et al, 2014), dorsal raphe (Shioiri et al, 1991), and dorsomedial hypothalamus (DMH; Acosta-Galvan et al, 2011), allowing these nuclei to convey nonphotic feedback to the SCN and thus adjusting circadian rhythmicity. Therefore, it is enticing to propose that the SCN is part of or central in a larger, complex neuronal network regulating circadian physiology and behavior.…”

VGF Peptide Profiles in Type 2 Diabetic Patients’ Plasma and in Obese Mice

“…In a group of patients treated for idiopathic intracranial hypertension, VGF immunoreactivity proved higher in cerebro-spinal fluid from obese, compared to non-obese subjects [ 21 ]. The number of neurons expressing both NPY and VGF was increased in the hypothalamic infundibular nucleus, but decreased in the nucleus of tractus solitarius of T2D patients, compared to non-diabetic controls [ 22 ].…”