Inward Glucose Transfer Accounts for Insulin‐Dependent Increase in Brain Glucose Metabolism Associated with Diet‐Induced Obesity

Abstract

Whole-body insulin sensitivity was reduced by more than 50% in the obesity group. During insulin stimulation, whole-brain insulin-induced increased glucose uptake was unaltered in lean animals but increased markedly in the animals with obesity. The increased glucose uptake reflected an increase in the inward transfer without changes in phosphorylation or outward brain transport. Connectivity was increased in the animals with obesity CONCLUSIONS: Diet-induced obesity is associated with an increase in insulin-stimulated brain glucose uptake as a consequence of a larger inward transfer. These changes occurred together with an increased connectivity in reference to regions associated with memory recollection.

Imaging of brain glucose uptake by PET in obesity and cognitive dysfunction: life-course perspective

“…Consistent with the above evidence, the injection of glucose in cerebral ventricles caused a suppression of hepatic glucose production in healthy mice (38), but a 4-week infusion failed to provoke any effect in type 2 diabetic rats (56). Controlled studies in pigs replicate the human findings, by showing no brain glucometabolic response to euglycemic hyperinsulinemia (compared to fasting state) in control pigs, as opposed to an elevated response in pigs fed a high-fat diet (57). Studies in Zucker fatty or diabetic rats have shown that their brain glucose uptake is chronically elevated under fasting and glucose loading conditions, lacking the excursion that normally signals the transition from a fasted to fed state (58).…”

The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns

“…More particularly, a blunted cerebrocortical response to insulin when MEG is applied [7], or a decreased suppression of hypothalamic blood flow after intranasal insulin administration in fMRI [9] have both been defined as cerebral (or central) insulin resistance. Our group and others have consistently reported increased metabolic rates in obese/insulin resistant subjects in [ 18 F]-FDG-PET studies, under conditions of euglycemic hyperinsulinemia [17][18][19]. Of note, MEG measures net effect of the ionic currents in neurons during synaptic transmission, BOLD fMRI evaluates cerebral blood flow and cerebral metabolic rate of oxygen, while [ 18 F]-FDG-PET quantifies glucose metabolic rates at the whole-brain level, and also in specific parts of the organ.…”

Pancreatic GLP-1r binding potential is reduced in insulin-resistant pigs

“…At 1 year of age, seven animals were made obese using a high-fat, high-sucrose diet (4.024 kcal/kg feed, 14.1% unsaturated fat, and 6.4% sucrose expressed in % dry matter) supplied at 150% of the recommended caloric intake for 5 months to induce morbid obesity. 20 The remaining seven animals were maintained on a low-fat, low-sucrose diet (2.275 kcal/kg feed, 4.1% unsaturated fat, and 3.5% sucrose expressed in % dry matter) for 5 months to limit body fat and ensure that total body weight was less than 40 kg. Immediately after this time, and while animals were provided with the same feeding regimen, PET-CT imaging of the abdominal area, using a GLP-1r PET radiotracer, was performed.…”

“…Between 3 and 4 weeks later, when the animals had recovered, insulin sensitivity was measured using a euglycemic–hyperinsulinemic clamp. 20 The insulin sensitivity index was calculated according to Malbert et al . 22 While the clamp was at its plateau phase, GLP-1r PET imaging was again performed to evaluate the impact of hyperinsulinemia on the GLP-1r binding potential.…”

“… 18 Finally, the mini-pig is known to develop obesity and insulin resistance rapidly in response to a high-fat/high-sucrose diet, 19 and euglycemic clamp steady-state conditions can be maintained for extended periods. 20 …”