Effects of glucosamine infusion on insulin secretion and insulin action in humans.

Monauni, Tiziano; Zenti, Maria Grazia; Cretti, A; Daniels, Marc C.; Targher, Giovanni; Caruso, Beatrice; Caputo, Marco; Mcclain, Don; Prato, Stefano Del; Giaccari, Andrea; Muggeo, Michele; Bonora, Enzo; Bonadonna, Riccardo C.

doi:10.2337/diabetes.49.6.926

Cited by 139 publications

(113 citation statements)

References 42 publications

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“…In muscle the level of UDP-GlcN was positively correlated with the decrease in glucose infusion rate [46]. Interestingly, in humans, glucosamine infusion impairs insulin-mediated glucose utilisation under hyperglycaemia, but not at euglycaemia [50] as it does in rats [6,7]. Taken together, it seems that glucosamine does model high-glucose-induced insulin resistance in muscle and it would be interesting to investigate whether high glucose also inhibits insulin-mediated capillary recruitment.…”

Section: Discussionmentioning

confidence: 95%

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

et al. 2005

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Aims/hypothesis: Glucose toxicity and glucosamine-induced insulin resistance have been attributed to products of glucosamine metabolism. In addition, endothelial cell nitric oxide synthase is inhibited by glucosamine. Since insulin has endothelial nitric-oxide-dependent vasodilatory effects in muscle, we hypothesise that glucosamine-induced insulin resistance in muscle in vivo is associated with impaired vascular responses including capillary recruitment. Materials and methods: Glucosamine (6.48 mg kg −1 min −1 for 3 h) was infused with or without insulin (10 mU kg −1 min −1 ) into anaesthetised rats under euglycaemic conditions. Results: Glucosamine infusion alone increased blood glucosamine (1.9±0.1 mmol/l) and glucose (5.4±0.2 to 7.7± 0.3 mmol/l) (p<0.05) but not insulin. Glucosamine induced both hepatic and muscle insulin resistance as evident from measures of glucose appearance and disposal as well as hindleg glucose uptake, which was inhibited by approx. 50% (p<0.05). Insulin-mediated increases in femoral arterial blood flow and capillary recruitment were completely blocked by glucosamine. Conclusion/interpretation: Glucosamine mediates a major impairment of insulin action in muscle vasculature associated with the insulin resistance of muscle. Further studies will be required to assess whether the impaired capillary recruitment contributes to insulin resistance.

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Section: Discussionmentioning

confidence: 95%

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

et al. 2005

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“…In a standard IVGTT analysed with minimal models, sampling is prolonged until 180-240 min, and glucose thresholds and basal insulin secretion rates are based on the levels attained at the end of the test [13,14]. Thus, glucose threshold and basal insulin secretion in the minimal model analysis of the IVGTTs included in the present study were higher than they might have been if sampling had been continued for an additional 120-180 min.…”

Section: Modelmentioning

confidence: 91%

“…In the last two decades, mathematical modelling of betacell-derived hormone concentration over time has progressed considerably, enabling one to safely distinguish between early and late phases of insulin secretion under experimental reference conditions, such as IVGTT [12][13][14] and hyperglycaemic clamp [11]. Recently, we introduced a parsimonious model of C-peptide secretion during OGTT as a tool for the physiological assessment of beta cell function [15].…”

Section: Introductionmentioning

confidence: 99%

Heritability of model-derived parameters of beta cell secretion during intravenous and oral glucose tolerance tests: a study of twins

et al. 2005

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Aims/hypothesis: The genetic architecture of model-derived parameters of beta cell function has never been assessed. Therefore, we estimated heritability (h 2 ) for model-derived phenotypes of insulin secretion in twins. Methods: Thirty-three monozygotic (MZ) and 23 dizygotic (DZ) twin pairs from the Finnish Twin Cohort Study underwent an OGTT (plasma glucose/C-peptide at 0, 30, 60, 90 and 120 min). A subset of the twin pairs (21 MZ/20 DZ) also underwent an IVGTT (frequent sampling of plasma glucose/insulin from 0 to 60 min) followed by a 160-min euglycaemic-hyperinsulinaemic clamp (45 mU · min −1 ·m −2 ). Mathematical modelling was applied to the IVGTT and the OGTT to assess first-phase (readily releasable insulin [RRI]) and second-phase (sigma) secretion (IVGTT), and a global index of beta cell performance (OGTT beta index). Intraclass correlation coefficients and genetic and non-genetic components for trait variances were computed to assess the h 2 of model-derived parameters. Results: The intraclass correlation coefficients in MZ twins were 0.78 for RRI, 0.67 for sigma and 0.57 for OGTT beta index. In DZ twins the correlation coefficients were 0.23, 0.32 and 0.42, respectively. Using the most parsimonious model for each trait, the h 2 -the proportion of variance accounted for by genetic factors -was 76% (95% CI: 53-88%) for RRI, 28% (34-80%) for sigma and 53% (26-72%) for OGTT beta index. Conclusions/ interpretation: Our findings demonstrate that model-derived parameters of insulin secretion have a substantial genetic component and may be used in the search for genetic determinants of beta cell function in humans.

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“…Intravenous administration of GlcN in rats induces much higher plasmatic concentrations than oral administration: infusion of 30.45 g of GlcN produced GlcN concentrations of ϳ1.42 mmol/liter (51). Because of the limited information regarding HBP flux, which is accelerated by GlcN infusion in humans, in vivo physiological dosing might be an important issue to be addressed in the future.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells

Hwang

Kwon

Kim

et al. 2017

Journal of Biological Chemistry

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Edited by Dennis R. VoelkerWe investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. However, GlcN suppressed NO/iNOS production under high glucose culture conditions. Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-␣ mRNAs under 25 mM glucose conditions yet did not inhibit upregulation under 5 mM glucose conditions. Glucose itself dose dependently increased LPS-induced iNOS expression. LPS-induced MAPK and IB-␣ phosphorylation did not significantly differ at normal and high glucose conditions. The activity of LPS-induced nuclear factor-B (NF-B) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. The NF-B inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. In addition, pyrrolidine dithiocarbamate inhibited NF-B DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess.

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Effects of glucosamine infusion on insulin secretion and insulin action in humans.

Cited by 139 publications

References 42 publications

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment

Heritability of model-derived parameters of beta cell secretion during intravenous and oral glucose tolerance tests: a study of twins

Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells

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