Pharmacologic or genetic activation of SIRT1 attenuates the fat-induced decrease in beta-cell function in vivo.

Background: There is evidence that sirtuin 1 (SIRT1), a key regulator of nutrient metabolism, increases β-cell secretory function. Excess circulating fat, as seen in obesity, has been shown to decrease β-cell function, an effect that may involve decreased SIRT1 activity. Consequently, SIRT1 activation may increase β-cell function in conditions of elevated plasma-free fatty acid levels.

Glucose-Induced β-Cell Dysfunction In Vivo: Evidence for a Causal Role of C-jun N-terminal Kinase Pathway.

Prolonged elevation of glucose can adversely affect β-cell function. Oxidative stress, which has been implicated in glucose-induced β-cell dysfunction, can activate c-jun N-terminal kinase (JNK). However, whether JNK is causal in glucose-induced β-cell dysfunction in vivo is unclear.

Evaluation of the specific effects of intranasal glucagon on glucose production and lipid concentration in healthy men during a pancreatic clamp.

Aim: To investigate the specific effects of intranasal glucagon (ING) on plasma glucose, endogenous glucose production (EGP) and lipid concentration.

Methods: We conducted a single-blind, randomized, crossover study at our academic investigation unit. Under pancreatic clamp conditions with tracer infusion, 1 mg ING or intranasal placebo (INP) was administered to 10 healthy men.

IKKβ inhibition prevents fat-induced beta cell dysfunction in vitro and in vivo in rodents.

Aims/hypothesis: We have previously shown that oxidative stress plays a causal role in beta cell dysfunction induced by fat. Here, we address whether the proinflammatory kinase inhibitor of (nuclear factor) κB kinase β (IKKβ), which is activated by oxidative stress, is also implicated.

Methods: Fat (oleate or olive oil) was infused intravenously in Wistar rats for 48 h with or without the IKKβ inhibitor salicylate.

A low-protein diet combined with low-dose endotoxin leads to changes in glucose homeostasis in weanling rats.

Severe malnutrition is a leading cause of global childhood mortality, and infection and hypoglycemia or hyperglycemia are commonly present. The etiology behind the changes in glucose homeostasis is poorly understood. Here, we generated an animal model of severe malnutrition with and without low-grade inflammation to investigate the effects on glucose homeostasis.