Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha O.; Iozzo, Patricia; Nuutila, Pirjo

doi:10.2337/db10-0940

Cited by 104 publications

(126 citation statements)

References 25 publications

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“…The fact that brain insulin may modulate glucose handling by this organ, in concert with brain IGF-I, may explain the difficulty in determining a role for circulating insulin in brain glucose handling. Because diabetes impacts the brain at biochemical, structural, and behavioral levels (6), it is possible that the action of brain insulin may be also altered, unveiling a role for circulating insulin in the diabetic state (2). Furthermore, a role for circulating I+I cannot be entirely ruled out yet, because, at least for the latter, neuronal activity triggers its entrance into the brain (19).…”

Section: Discussionmentioning

confidence: 99%

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Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

et al. 2016

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Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes.

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Section: Discussionmentioning

confidence: 99%

“…Only under pathological circumstances, such as diabetes, do brain glucoregulatory actions of insulin manifest (2). Therefore, mechanisms of neurovascular coupling, whereby active brain regions locally increase glucose and oxygen uptake, are not considered to involve insulin under physiological circumstances.…”

mentioning

confidence: 99%

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

et al. 2016

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“…Another study, however, in which a hyperinsulinaemic‐euglycaemic clamp procedure was used, showed that insulin had no effect on CBF when healthy subjects and subjects with impaired glucose tolerance were compared 58. Van Golen et al.…”

Section: Central Nervous System Hypothesismentioning

confidence: 99%

Weight‐sparing effect of insulin detemir: a consequence of central nervous system‐mediated reduced energy intake?

Russell‐Jones

Danne

Hermansen

et al. 2015

Diabetes Obesity Metabolism

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Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight‐sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter‐regulatory response to insulin through restoration of the hepatic–peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight‐sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.

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“…High concentrations of insulin receptors have been reported in the cerebral cortex and hippocampus (52), so insulin could have direct effects on activity and cognitive function in the CNS (22). It influences cognitive functions by modulating neurotransmitter release and synaptic plasticity (24). Also, it modulates acetylcholine and norepinephrine levels in brain and influences cognitive function (19,26).…”

Section: Discussionmentioning

confidence: 99%

Intranasal insulin treatment improves memory and learning in a rat amyloid-beta model of Alzheimer’s disease

Farzampour¹,

Majdi²,

Sadigh-Eteghad³

2016

Physiology International

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Recently, insulin has been used as a pro-cognitive agent for the potential treatment of Alzheimer's disease (AD), because of its ability to cross the brain-blood barrier (BBB) by a saturable transport system. This study has been designed to evaluate the effects of intranasal insulin regimen, as a bypass system of BBB, on spatial memory in amyloid-beta (Aβ) model of AD in rat. Unilateral infusion of Aβ 25-35 (10 nmol/2 μl/rat) into the lateral ventricular region of brain was used to produce a rat model of AD. After a 24-h recovery period, rats received insulin or vehicle via intraperitoneal or intranasal route (0.1, 0.2, and 0.3 IU) for 14 days. Memory function in rats was assessed by Morris water maze test, with 5 days of training and consequent probe test protocol. Different doses of intraperitoneal insulin did not have a significant effect on learning and memory in AD rats. However, intranasal insulin at doses of 0.2 and 0.3 IU improved the learning and memory in Aβ-received rats.In conclusion, intranasal insulin as a non-invasive strategy improves spatial learning and memory in AD model.

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Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

Cited by 104 publications

References 25 publications

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

Weight‐sparing effect of insulin detemir: a consequence of central nervous system‐mediated reduced energy intake?

Intranasal insulin treatment improves memory and learning in a rat amyloid-beta model of Alzheimer’s disease

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