Correlates of insulin clearance in apparently healthy non-obese Japanese men

Tamura, Yasuaki; Takeno, Kageumi; Kakehi, Saori; Fukushima, Takashi; Furukawa, Yasushi; Nishitani‐Yokoyama, Miho; Shimada, Kazunori; Daida, Hiroyuki; Aoki, Shigeki; Giacca, Adria; Kanazawa, Akio; Kawamori, Ryuzo; Watada, Hirotaka

doi:10.1038/s41598-017-01469-x

Cited by 31 publications

(28 citation statements)

References 45 publications

(72 reference statements)

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“…In our cohort of healthy and non‐obese participants, we found that insulin MCR correlated significantly with several adverse metabolic parameters, such as total body fat mass, fat mass percentage and glucose Rd/SS Ins . Similar findings have also been reported in healthy and non‐obese Japanese individuals with low insulin MCR. Thus, the lower insulin MCR could represent the initial event in the natural history of IR and obesity pathogenesis among Indian individuals.…”

Section: Discussionsupporting

confidence: 85%

“…These metabolic parameters have not been adequately studied in non‐obese Indians and Chinese. Similarly, hyperinsulinemia and the impaired insulin metabolic clearance rate (MCR) might be a harbinger of worsenining IR and future cardiometabolic disorders, even in healthy individuals with non‐obese BMI. However, the influence of impaired insulin MCR on metabolic health in these two ethnic groups remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive assessment of insulin resistance in non‐obese Asian Indian and Chinese men

Tan

Yew

Chacko

et al. 2018

J of Diabetes Invest

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Aims/IntroductionIndian individuals are more insulin resistant (IR) than Chinese individuals, even among those with a non‐obese body mass index (BMI). However, BMI often underestimates body fat in Indian individuals, and it remains unclear whether Indians would remain more IR than Chinese individuals when both BMI and body fat are equally matched.Materials and MethodsUsing the hyperinsulinemic‐euglycemic clamp with stable‐isotope infusion, we comprehensively assessed IR between 13 non‐obese Indian men with 13 Chinese men matched for age, BMI and body fat. We further compared the differences in insulin metabolic clearance rate (MCR) between the two groups and its relationship with various metabolic parameters. The response of lipid and amino acid metabolism to insulin stimulation was also evaluated using metabolomic profiling.ResultsThe rates of endogenous glucose production during fasting were similar, and endogenous glucose production was completely suppressed during insulin clamp for both ethnic groups. Glucose disappearance during insulin clamp was also similar between the two groups, even after accounting for differences in insulin concentration. Metabolomic profiles of amino acids and various acylcarnitines were similar during both fasting and insulin clamp. However, plasma insulin during clamp was significantly higher in Indian men, indicating that insulin MCR was lower. Insulin MCR correlated significantly with total adiposity and skeletal muscle insulin sensitivity.ConclusionWhen equally matched for body fat, non‐obese Indian men had similar skeletal muscle insulin sensitivity and endogenous glucose production to Chinese men. The effects of insulin on lipid and amino acid metabolism were also similar. Low insulin MCR is associated with greater adiposity and lower skeletal muscle insulin sensitivity.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Comprehensive assessment of insulin resistance in non‐obese Asian Indian and Chinese men

Tan

Yew

Chacko

et al. 2018

J of Diabetes Invest

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“…1), supporting a link between hepatic insulin clearance and hepatic insulin sensitivity. An inverse association between insulin clearance and basal as well as insulin-suppressed hepatic glucose production has also been demonstrated in cross-sectional studies (46).…”

Section: Hepatic Fat Content and Insulin Clearancementioning

confidence: 70%

Hepatic Insulin Clearance in Regulation of Systemic Insulin Concentrations—Role of Carbohydrate and Energy Availability

et al. 2018

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Hyperinsulinemia is the hallmark of insulin resistance in obesity, and the relative importance of insulin clearance, insulin resistance, and insulin hypersecretion has been widely debated. On the basis of recent experimental evidence, we summarize existing evidence to suggest hepatic insulin clearance as a major and immediate regulator of systemic insulin concentrations responding within days to altered dietary energy and, in particular, carbohydrate intake. Hepatic insulin clearance seems to be closely associated with opposite alterations in hepatic lipid content and glucose production, providing a potential mechanistic link to hepatic insulin sensitivity. The molecular regulation of insulin clearance in the liver is likely to involve changes in insulin binding and receptor internalization in response to the dietary alterations, the molecular mechanisms of which await further research.

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“…When insulin resistance was induced by dietary fat, normal dogs responded by enhancing b-cell function by approximately 20% and reducing insulin clearance by approximately 50%; the decreased insulin clearance preceded b-cell compensation (48). Therefore, decreased insulin clearance is hypothesized to be an important compensatory mechanism for insulin-resistant states, such as type 2 diabetes, as it reduces the burden on b-cells to produce additional insulin (49,50). In our study, ghrelin, with or without Ex9, decreased meal-related insulin clearance and insulin sensitivity (OGIS) compared with saline.…”

Section: Salinementioning

confidence: 99%

Interaction of GLP-1 and Ghrelin on Glucose Tolerance in Healthy Humans

Page

Gastaldelli

Gray³

et al. 2018

Diabetes

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Emerging evidence supports the importance of ghrelin to defend against starvation-induced hypoglycemia. This effect may be mediated by inhibition of glucose-stimulated insulin secretion as well as reduced insulin sensitivity. However, administration of ghrelin during meal consumption also stimulates the release of glucagon-like peptide 1 (GLP-1), an incretin important in nutrient disposition. The objective of this study was to evaluate the interaction between ghrelin and GLP-1 on parameters of glucose tolerance following a mixed-nutrient meal. Fifteen healthy men and women completed the study. Each consumed a standard meal on four separate occasions with a superimposed infusion of ) saline,) ghrelin, ) the GLP-1 receptor antagonist exendin(9-39) (Ex9), or) combined ghrelin and Ex9. Similar to previous studies, infusion of ghrelin caused glucose intolerance, whereas Ex9 had a minimal effect. However, combined ghrelin and Ex9 resulted in greater postprandial glycemia than either alone, and this effect was associated with impaired β-cell function and decreased glucose clearance. These findings suggest that in the fed state, stimulation of GLP-1 mitigates some of the effect of ghrelin on glucose tolerance. This novel interaction between gastrointestinal hormones suggests a system that balances insulin secretion and glucose disposal in the fed and fasting states.

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Correlates of insulin clearance in apparently healthy non-obese Japanese men

Cited by 31 publications

References 45 publications

Comprehensive assessment of insulin resistance in non‐obese Asian Indian and Chinese men

Comprehensive assessment of insulin resistance in non‐obese Asian Indian and Chinese men

Hepatic Insulin Clearance in Regulation of Systemic Insulin Concentrations—Role of Carbohydrate and Energy Availability

Interaction of GLP-1 and Ghrelin on Glucose Tolerance in Healthy Humans

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