Central effects of insulin detemir on feeding, body weight, and metabolism in rats

Vasselli, Joseph R.; Pi‐Sunyer, F. Xavier; Wall, D.G.; John, Catherine S.; Chapman, Colin D.; Currie, Paul J.

doi:10.1152/ajpendo.00111.2016

Cited by 6 publications

(8 citation statements)

References 35 publications

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“…42,43 The effect of central insulin administration on body weight is in contrast to peripheral administration of insulin, which has anabolic effects. 44 The central anorectic effects of insulin have subsequently been replicated in rats [45][46][47][48] and mice. [49][50][51] Acute administration of insulin into the brain decreases food intake dose-dependently 48,52 and reduces body weight for a period of approximately 24-48 hours following infusion, 29,47 whereas chronic administration of cerebral insulin reduces both food intake and body weight over a longer time period.…”

Section: In Sulin ' S Role In Food Intakementioning

confidence: 99%

“…44 The central anorectic effects of insulin have subsequently been replicated in rats [45][46][47][48] and mice. [49][50][51] Acute administration of insulin into the brain decreases food intake dose-dependently 48,52 and reduces body weight for a period of approximately 24-48 hours following infusion, 29,47 whereas chronic administration of cerebral insulin reduces both food intake and body weight over a longer time period. 36,53,54 Rodent studies examining the metabolic and behavioural effects of intracranial insulin infusion usually employ i.c.v.…”

Section: In Sulin ' S Role In Food Intakementioning

confidence: 99%

“…100 Intracerebroventricular administration of insulin results in an up-regulation of c-Fos (a marker of neuronal activity) in the PVN, 101 whereas an injection of insulin directed at the PVN decreases food intake and increases energy expenditure. 46,47 Some evidence suggests that insulin exerts hypophagic effects through an indirect interaction between the ARC and Y1 (one of the five Y receptors that mediate the actions of NPY) and MC4 receptors located on PVN neurones. 102 For example, through the use of mice that have a Cre-mediated deletion of MC4 receptors, it was shown that re-expression of MC4 receptors in the PVN reduced obesity and normalised hyperinsulinaemia.…”

Section: The Role Of Hyp Othal Ami C N Uclei In Feed Ing and Energy Homeos Ta S Ismentioning

confidence: 99%

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The regulation of food intake by insulin in the central nervous system

Begg

2021

J Neuroendocrinology

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Animals must find and consume food to meet intake demands and maintain energy balance. The regulation of food intake is dependent on many factors, including environment, energy stores, peripheral hormone secretion, and their feedback to homeostatic and hedonic brain circuits. Importantly, disruption to the balance of food intake and energy expenditure leads to weight and metabolism-related pathologies, including obesity and type II diabetes. 1 As a result of the worldwide obesity epidemic of recent decades, an improved understanding of the regulation of food intake via integration of peripheral signals and central nervous system (CNS) circuits may lead to novel treatment approaches for obesity.Insulin, a pancreatic hormone released in response to elevated blood glucose, was first discovered by Banting and Best in the pancreatic extracts of dogs 100 years ago. 2 Insulin is primarily known as a peripheral regulator of blood glucose levels and, hence, has been used as a treatment for both type I and type II diabetes mellitus, diseases affecting over 450 million people globally. 3 Following an increase in blood glucose levels (ie, when a meal is consumed), the release of insulin is stimulated, which circulates in the bloodstream and binds to insulin receptors on cell membranes in tissues such as the liver, muscle and adipose tissue. This binding of insulin at its receptor results in phosphorylation of insulin receptor substrate proteins 1 and 2 (IRS1 and IRS2), ultimately activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. 4 PI3K activation

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Section: In Sulin ' S Role In Food Intakementioning

confidence: 99%

Section: In Sulin ' S Role In Food Intakementioning

confidence: 99%

Section: The Role Of Hyp Othal Ami C N Uclei In Feed Ing and Energy Homeos Ta S Ismentioning

confidence: 99%

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The regulation of food intake by insulin in the central nervous system

Begg

2021

J Neuroendocrinology

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“…In this same report, ArcN Ex-4 reliably suppressed the increase in RER found after co-infusion of ghrelin and NPY (Abtahi et al, 2016). As a result, and in order to further investigate the metabolic function of hypothalamic GLP-1, ghrelin, and NPY, in the present study we targeted the PVN, given the well-established role of th is nucleus in regulating energy metabolism and substrate oxidation (Currie et al, 2010; Gao et al, 2018; Thomas et al, 2015; Vasselli et al, 2017). Specifically, the overall objective of the current report was to initially compare the impact of acyl and des-acyl ghrelin on energy substrate utilization.…”

Section: Introductionmentioning

confidence: 99%

Exendin-4 antagonizes the metabolic action of acylated ghrelinergic signaling in the hypothalamic paraventricular nucleus

Abtahi

Howell

Salvucci

et al. 2019

General and Comparative Endocrinology

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In the current study we investigated the interaction of hypothalamic paraventricular nucleus (PVN) glucagon-like peptide-1 (GLP-1) and ghrelin signaling in the control of metabolic function. We first demonstrated that acylated ghrelin injected directly into the PVN reliably altered the respiratory exchange ratio (RER) of adult male Sprague Dawley rats. All testing was carried out during the initial 2 h of the nocturnal cycle using an indirect open circuit calorimeter. Results indicated that acylated ghrelin induced a robust increase in RER representing a shift toward enhanced carbohydrate oxidation and reduced lipid utilization. In contrast, treatment with comparable dosing of des-acyl ghrelin failed to significantly impact metabolic activity. In separate groups of rats we subsequently investigated the ability of exendin-4 (Ex-4), a GLP-1 analogue, to alter acylated ghrelin’s metabolic effects. Rodents were treated with either systemic or direct PVN Ex-4 followed by acyl ghrelin microinjection. While our results showed that both systemic and PVN administration of Ex-4 significantly reduced RER, importantly, Ex-4 pretreatment itself reliably inhibited the impact of ghrelin on RER. Overall, these findings provide increasingly compelling evidence that GLP-1 and ghrelin signaling interact in the neural control of metabolic function within the PVN.

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“…This finding is in contradistinction to the findings in rats, where whole body energy expenditure is significantly increased with insulin detemir after 72 hours as compared with regular human insulin. 22 In the same study, there was reduced food intake in insulin detemir group compared to regular human insulin. 22 Previous studies have shown an effect of insulin detemir to reduce food intake as compared to NPH insulin, but NPH is also known to cause more frequent hypoglycemia compared to insulin glargine or detemir.…”

Section: Discussionmentioning

confidence: 84%

Effects of insulin detemir versus insulin glargine on food intake and satiety factors in type 1 diabetes

Fallahi¹,

Garimella²,

Mitchell³

et al. 2021

JDMDC

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Background: Insulin detemir is long-acting insulin analog that is weight-neutral compared with other long-acting insulins in patients with type 1 diabetes. One mechanism for this may be an effect of insulin detemir to enhance satiety. We hypothesized that type 1 diabetes patients on insulin detemir will eat fewer calories when presented with a standardized buffet meal following a 24-hour fast as compared to those on insulin glargine. Methods: Ten subjects with C-peptide negative type 1 diabetes participated in a randomized, double-blind crossover study in which they received equivalent doses of either insulin detemir or insulin glargine twice daily for at least 3 weeks. They were subsequently admitted to the UNM Clinical Research Unit for a 24-hour fast, after which they were allowed to eat to satiety from a standardized buffet. Caloric consumption, hunger score and body compositions were measured. Leptin, Ghrelin and Peptide YY were assessed at baseline, after 24-hour fast, and after ingestion of the meal. Results: Subjects were aged 35±11 years, had diabetes for 18±11 years, had A1c levels of 8±1% and BMI of 30±8 kg/m2. Short acting insulin doses were higher for subjects receiving insulin detemir versus insulin glargine (p<0.001). Hunger scores, total energy ingested following the 24-hour fast, and Resting Energy Expenditure did not significant differ between the two study conditions. Conclusion: The weight-neutrality of insulin detemir in type 1 diabetes is not attributable to reduced caloric intake following a fast, or to serum satiety factors.

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Central effects of insulin detemir on feeding, body weight, and metabolism in rats

Cited by 6 publications

References 35 publications

The regulation of food intake by insulin in the central nervous system

The regulation of food intake by insulin in the central nervous system

Exendin-4 antagonizes the metabolic action of acylated ghrelinergic signaling in the hypothalamic paraventricular nucleus

Effects of insulin detemir versus insulin glargine on food intake and satiety factors in type 1 diabetes

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