GIP’s involvement in the pathophysiology of type 2 diabetes

Christensen, Mikkel B.; Gasbjerg, Lærke S.; Heimbürger, Sebastian M. Nguyen; Stensen, Signe; Vilsbøll, Tina; Knop, Filip K.

doi:10.1016/j.peptides.2019.170178

Cited by 21 publications

(12 citation statements)

References 106 publications

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“…We did not include a control group in this study, but the magnitude of the saline-placebo-adjusted responses to GIP seem comparable to the 25% reduction observed after 1 hour in metabolically healthy individuals under similar research conditions [ 8 ]. The slightly greater CTX reduction in the present experiments occurs despite the fact that GIP only leads to a 1.4-fold increase in insulin secretion rate in this cohort of patients T2D [ 17 ], which is much lower than the 2.4-fold increase observed in metabolically healthy young individuals [ 18 ]. Thus, our findings seem to refute that the effects of GIP on bone resorption is impaired in patients with T2D, unlike the insulinotropic effect of GIP [ 17 ].…”

Section: Discussionmentioning

confidence: 60%

“…Second, it is well established that the insulin-releasing property of GIP is severely impaired in patients with T2D (i.e., they have a reduced incretin effect) [ 16 , 17 ]. The reduced insulinotropic effect of GIP develops secondary to the diabetic state [ 18 ], and may be due to the chronic hyperglycemia and subsequent GIP-receptor downregulation on pancreatic beta cells [ 19 , 20 ]. Furthermore, the insulinotropic effect of GIP is highly glucose-dependent (i.e., almost absent during fasting and hypoglycemia) [ 17 , 21 ].…”

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confidence: 99%

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Glucose-Dependent Insulinotropic Polypeptide (GIP) Reduces Bone Resorption in Patients With Type 2 Diabetes

Christensen

Lund

Jørgensen

et al. 2020

Journal of the Endocrine Society

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Context In healthy individuals, GIP enhances insulin secretion and reduces bone resorption by up to 25% estimated by absolute placebo-corrected changes in carboxy-terminal type 1 collagen crosslinks (CTX) during GIP and glucose administration. In patients with type 2 diabetes (T2D), GIP’s insulinotropic effect is impaired and effects on bone may be reduced. Objective To investigate GIP’s effect on bone biomarkers in patients with T2D. Design Randomized, double-blinded, crossover study investigating six interventions. Patients Twelve male patients with T2D. Interventions A primed continuous 90-minute GIP-infusion (2 pmol/kg/min) or matching placebo (saline) administered at three plasma glucose (PG) levels i.e. paired days with ‘insulin-induced hypoglycemia’ (PG lowered to 3 mmol/l), ‘fasting hyperglycemia’ (mean PG ~8 mmol/l), or ‘aggravated hyperglycemia’ (mean PG ~12 mmol/l). Main Outcome Measures Bone biomarkers: CTX, Procollagen Type 1 N-terminal propeptide (P1NP) and PTH. Results On days with ‘insulin-induced hypoglycemia’ CTX was suppressed by up to 40±15% during GIP administration compared to 12±11% during placebo infusion (P<0.0001). On days with ‘fasting hyperglycemia’ CTX was suppressed by up to 36±15% during GIP administration, compared to 0±9% during placebo infusion (P<0.0001). On days with ‘aggravated hyperglycemia’ CTX was suppressed by up to 47±23% during GIP administration compared to 10±9% during placebo infusion (P=0.0005). At all glycemic levels, P1NP and PTH concentrations were similar between paired days after 90 minutes. Conclusions Short-term GIP infusions reduce bone resorption by more than a third (estimated by absolute placebo-corrected CTX reductions) in patients with T2DM suggesting preserved bone effects of GIP in these patients.

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Section: Discussionmentioning

confidence: 60%

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confidence: 99%

Glucose-Dependent Insulinotropic Polypeptide (GIP) Reduces Bone Resorption in Patients With Type 2 Diabetes

Christensen

Lund

Jørgensen

et al. 2020

Journal of the Endocrine Society

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“…These findings were subsequently confirmed by many studies (31). Many investigators have therefore proposed the concept of "entero-osseous axis" (32), which means that bone metabolism may be regulated by incretin.…”

Section: Discussionmentioning

confidence: 81%

Relationship between glucagon-like peptide-1 receptor gene polymorphism and bone mineral density in postmenopausal women in Shanghai

Zhang

Sun

et al. 2020

Ann Palliat Med

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Background: Glucagon-like peptide-1 receptor (GLP-1R) agonists are able to inhibit bone resorption to a certain extent and improve bone formation. GLP-1R single nucleotide polymorphism (SNP) is related to its activity, but the relationship between GLP-1R SNP and osteoporosis in postmenopausal women was still unclear. This study was to investigate the association between GLP-1R SNP and bone mineral density (BMD) in postmenopausal women in Shanghai.Methods: Eight SNPs of GLP-1R were detected (rs3765467, rs1042044, rs2268657, rs6923761, rs2268641, rs2295006, rs4714210 and rs10305420) in 884 postmenopausal women in Shanghai. The correlation between GLP-1R SNP and BMD was further assessed. Results:The A/A genotype of rs2295006 was negatively related to lumbar vertebrae 1-4 BMD (P<0.05).Allele A was negatively related to hip BMD (P<0.05). There was a negative correlation between haplotype CGAGCCA and lumbar BMD, and a positive correlation between haplotype CGGGCTA and lumbar BMD.The remaining seven GLP-1R SNPs had no relationship with BMD. Conclusions:The rs2295006 of GLP-1R is related to the BMD of postmenopausal women in Shanghai, China.

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“…Recent studies have demonstrated that the prevalence of diabetes mellitus has increased from 451 million people in 2017 and is estimated to reach 693 million by 2045 3 . Most of the patients (more than 90%) with elevated blood glucose levels are diagnosed with type 2 DM (T2DM), which is pathologically insulin‐independent 4 . T2DM is characterized by the resistance of hepatocytes, adipocytes, and myocytes to insulin, resulting in progressive cell dysfunction and hyperglycaemia 2 .…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive insight into the effect of chromium supplementation on oxidative stress indices in diabetes mellitus: A systematic review

Kooshki

Tutunchi

Vajdi

et al. 2021

Clin Exp Pharma Physio

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Diabetes mellitus is a metabolic disorder defined as an increase in blood glucose levels (hyperglycaemia) and insufficient production or action of insulin produced by the pancreas. Chronic hyperglycaemia leads to increased reactive oxygen species (ROS) production and oxidative stress, which consequently results in insulin resistance, beta cell degeneration, dyslipidaemia, and glucose intolerance in diabetic patients. Chromium has an essential role in the metabolism of proteins, lipids, and carbohydrates through increasing insulin efficiency. This systematic review aimed to evaluate chromium supplementation's potential roles in oxidative stress indices in diabetes mellitus. A systematic search was performed in PubMed, Scopus, Google Scholar, Cochrane, and Science Direct databases until November 2020. All clinical trials and animal studies that assessed chromium's effect on oxidative stress indices in diabetes mellitus and were published in English‐language journals were included. Finally, only 33 out of 633 articles met the required criteria for further analysis. Among 33 papers, 25 studies were performed on animals, and eight investigations were conducted on humans. Twenty‐eight studies of chromium supplementation lead to reducing oxidative stress indices. Also, 23 studies showed that chromium supplementation markedly increased antioxidant enzymes' activity and improved levels of antioxidant indices. In conclusion, chromium supplementation decreased oxidative stress in diabetes mellitus. However, further clinical trials are suggested in a bid to determine the exact mechanisms.

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GIP’s involvement in the pathophysiology of type 2 diabetes

Cited by 21 publications

References 106 publications

Glucose-Dependent Insulinotropic Polypeptide (GIP) Reduces Bone Resorption in Patients With Type 2 Diabetes

Glucose-Dependent Insulinotropic Polypeptide (GIP) Reduces Bone Resorption in Patients With Type 2 Diabetes

Relationship between glucagon-like peptide-1 receptor gene polymorphism and bone mineral density in postmenopausal women in Shanghai

A Comprehensive insight into the effect of chromium supplementation on oxidative stress indices in diabetes mellitus: A systematic review

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