Central nervous pathways of insulin action in the control of metabolism and food intake

Kullmann, Stephanie; Kleinridders, André; Small, Dana M.; Fritsche, Andreas; Häring, Hans‐Ulrich; Preißl, Hubert; Heni, Martin

doi:10.1016/s2213-8587(20)30113-3

Cited by 148 publications

(162 citation statements)

References 123 publications

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“…These mechanisms are supported by balanced adjustments in insulin secretion to keep the metabolic system under tight control. The changes in insulin secretion and action are highly coordinated by the central nervous system (CNS) to ensure appropriate substrate switching between tissues to meet metabolic needs, such as in the postabsorptive to postprandial transition [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach

et al. 2021

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Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.

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Section: Introductionmentioning

confidence: 99%

Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach

et al. 2021

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show abstract

Section: Introductionmentioning

confidence: 99%

“…Dopamine might mediate the central and peripheral insulin sensitivities, which indicate the relationship between NDs and glucose metabolism. 4 Furthermore, some kinds of diabetes drugs have been reported to have important impacts on the pathogenesis of these two major kinds of NDs. As a top-tier drug for the treatment of type 2 diabetes mellitus (T2DM), the role of metformin in dementia and PD is highly inconsistent, both in animal models and in clinical studies.…”

mentioning

confidence: 99%

Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis

Ping

Jiang

2020

BMJ Open Diab Res Care

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Background and aimsAging becomes a growing global concern with an increased risk of neurodegenerative diseases (NDs) that mainly consist of cognitive decline and Parkinson disease (PD). As the most commonly prescribed antidiabetic drug, metformin has been shown to have inconsistent roles in the incidence of NDs. We performed a systematic review and meta-analysis of observational studies to evaluate the effect of metformin exposure on onset of NDs.MethodsThe observational studies that investigated the associations between metformin and the incidence of NDs were searched in MEDLINE, Embase and Cochrane Library databases. A random-effect model was performed using STATA to calculate the combined ORs.ResultsIn total, 23 comparisons out of 19 studies with 285 966 participants were included. Meta-analysis found there was no significant effect on incidence of all the subtypes of NDs with metformin exposure (OR 1.04, 95% CI 0.92 to 1.17). However, metformin monotherapy was associated with a significantly increased risk of PD incidence compared with non-metformin users or glitazone users (OR 1.66, 95% CI 1.14 to 2.42).ConclusionMetformin has failed to demonstrate a beneficial effect on NDs. In addition, it may increase the risk of PD development. In light of current results, how metformin would impact NDs, especially the potential risk of PD, needs to be scrutinized. The underlying mechanisms are vital to achieve some more profound understanding on the regimen.Trial registration numberCRD 42019133285.

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“…Furthermore, in a crosssectional experiment, good hypothalamic insulin responsiveness was associated with lesser visceral fat mass, while no correlation was detected with subcutaneous fat mass. However, origins and mechanisms of brain insulin resistance remain elusive [2].…”

mentioning

confidence: 99%

Brain insulin sensitivity is linked to body fat distribution—the positron emission tomography perspective

Rebelos

Nummenmaa

Dadson

et al. 2020

Eur J Nucl Med Mol Imaging

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Central nervous pathways of insulin action in the control of metabolism and food intake

Cited by 148 publications

References 123 publications

Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach

Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach

Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis

Brain insulin sensitivity is linked to body fat distribution—the positron emission tomography perspective

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