type 2 diabetes

Targeting the brain to improve obesity and type 2 diabetes

The increasing prevalence of obesity and type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating energy homeostasis to accelerate the identification of new medications. Recent reports indicate that obesity medication, 5-hydroxytryptamine (5-HT, serotonin)2C receptor (5-HT2CR) agonist lorcaserin improves glycemic control in association with weight loss in obese patients with T2D. We examined whether lorcaserin has a direct effect on insulin sensitivity and how this effect is achieved. We clarify that lorcaserin dose-dependently improves glycemic control in a mouse model of T2D without altering body weight. Examining the mechanism of this effect, we reveal a necessary and sufficient neurochemical mediator of lorcaserin’s glucoregulatory effects, via activation of brain pro-opiomelanocortin (POMC) peptides. We observed that lorcaserin reduces hepatic glucose production and improves insulin sensitivity. These data suggest that lorcaserin’s action within the brain represents a mechanistically novel treatment for T2D: findings of significance to a prevalent global disease.

A metabolic function of the hippocampal sharp wave-ripple

The hippocampal formation has been implicated in both cognitive functions as well as the sensing and control of endocrine states. To identify a candidate activity pattern which may link such disparate functions, we simultaneously measured electrophysiological activity from the hippocampus and interstitial glucose concentrations in the body of freely behaving rats. We found that clusters of sharp wave-ripples (SPW-Rs) recorded from both dorsal and ventral hippocampus reliably predicted a decrease in peripheral glucose concentrations within ~10 minutes. This correlation was less dependent on circadian, ultradian, and meal-triggered fluctuations, it could be mimicked with optogenetically induced ripples, and was attenuated by pharmacogenetically suppressing activity of the lateral septum, the major conduit between the hippocampus and subcortical structures. Our findings demonstrate that a novel function of the SPW-R is to modulate peripheral glucose homeostasis and offer a mechanism for the link between sleep disruption and blood glucose dysregulation seen in type 2 diabetes and obesity.

Hippocampal neurovascular coupling and spatial working memory impairment in a rodent model of type 2 diabetes: impact of dietary nitrate intervention

Regulation of the apoptosis/autophagy switch by propionic acid in ventromedial hypothalamus of rats with type 2 diabetes mellitus

Aggression control by type 2 diabetes risk gene Dusp8

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Antioxidant effect of combined administration of metformin and propionate in a rat model of type 2 diabetes mellitus

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Impact of type 2 diabetes and high-intensity interval exercise on neurogenesis, angiogenesis, and the accumulation of lipid droplets in the hippocampus

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Non-canonical anti-inflammatory effects of sitagliptin, a drug for type 2 diabetes, in microglia

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Prediabetes and type 2 diabetes affect tau phosphorylation patterns in murine models of Alzheimer’s disease

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Structural and functional alterations in the retina of a model of Alzheimer’s disease and type 2 diabetes

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Subchronic administration of the antidiabetic drug metformin mitigates cognitive impairments in a mouse model of type 2 diabetes mellitus

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