GIP-induced vasodilation in human adipose tissue involves capillary recruitment

Asmar, Meena; Asmar, Ali; Simonsen, Lene; Dela, Flemming; Holst, Jens J.; Bülow, Jens

doi:10.1530/ec-19-0144

Cited by 25 publications

(24 citation statements)

References 37 publications

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“…The involvement of GLP‐1 and its metabolites, especially GLP‐1 (9‐36), in the improvement of vasodilatory response of endothelial cells is reported, in detail, by Li et al 66 GIP infusion during a hyperglycaemia/hyperinsulinaemia clamp (mimicking postprandial levels) resulted, in healthy, but not in men with obesity, in increased blood flow in subcutaneous AT that was accompanied by capillary recruitment. Such effect was not elicited by insulin alone, which is also in accordance with GIP stimulation of insulin‐induced glucose uptake and fatty acids storage 67 . The precise mechanism underlying such effect is still unknown, but it might involve nitric oxide‐dependent mechanisms, because GIP was shown to induce nitric oxide raise in bovine aortic endothelial cells 68 .…”

Section: Crosstalk Between Gut and Atsupporting

confidence: 59%

“…Such effect was not elicited by insulin alone, which is also in accordance with GIP stimulation of insulin-induced glucose uptake and fatty acids storage. 67 The precise mechanism underlying such effect is still unknown, but it might involve nitric oxide-dependent mechanisms, because GIP was shown to induce nitric oxide raise in bovine aortic endothelial cells. 68 Moreover, it is known that nitric oxide stimulates LPL activity in cultured pre-adipocytes.…”

Section: Modulation Of At Plasticity: Adipogenesis and Angiogenesismentioning

confidence: 99%

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Gut–adipose tissue crosstalk: A bridge to novel therapeutic targets in metabolic syndrome?

Rosendo‐Silva

Matafome

2020

Obesity Reviews

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The gut is one of the main endocrine organs in our body, producing hormones acknowledged to play determinant roles in controlling appetite, energy balance and glucose homeostasis. One of the targets of such hormones is the adipose tissue, a major energetic reservoir, which governs overall metabolism through the secretion of adipokines. Disturbances either in nutrient and metabolic sensing and consequent miscommunication between these organs constitute a key driver to the metabolic complications clustered in metabolic syndrome. Thus, it is essential to understand how the disruption of this crosstalk might trigger adipose tissue dysfunction, a strong characteristic of obesity and insulin resistance. The beneficial effects of metabolic surgery in the amelioration of glucose homeostasis and body weight reduction allowed to understand the potential of gut signals modulation as a treatment for metabolic syndrome-related obesity and type 2 diabetes. In this review, we cover the effects of gut hormones in the modulation of adipose tissue metabolic and endocrine functions, as well as their impact in tissue plasticity. Furthermore, we discuss how the modulation of gut secretome, either through surgical procedures or pharmacological approaches, might improve adipose tissue function in obesity and metabolic syndrome.

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Section: Crosstalk Between Gut and Atsupporting

confidence: 59%

Section: Modulation Of At Plasticity: Adipogenesis and Angiogenesismentioning

confidence: 99%

Gut–adipose tissue crosstalk: A bridge to novel therapeutic targets in metabolic syndrome?

Rosendo‐Silva

Matafome

2020

Obesity Reviews

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“…Indeed, in preclinical in vivo and in vitro models, GIP increases adipocyte LPL expression 22,23 . Although the mechanisms are not fully understood, infusion of GIP and GIP receptor antagonists in humans suggests that GIP receptor activation increases adipose tissue blood flow and promotes adipose tissue lipid uptake 24,25 . Thus, GIP receptor agonism in adipocytes may be a key regulator of postprandial lipid clearance and potentially overall lipid homeostasis.…”

Section: Introductionmentioning

confidence: 99%

The dual glucose‐dependent insulinotropic peptide and glucagon‐like peptide‐1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes

Wilson

Nikooienejad

Robins

et al. 2020

Diabetes Obesity Metabolism

103

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Aim: To better understand the marked decrease in serum triglycerides observed with tirzepatide in patients with type 2 diabetes, additional lipoprotein-related biomarkers were measured post hoc in available samples from the same study. Materials and Methods: Patients were randomized to receive once-weekly subcutaneous tirzepatide (1, 5, 10 or 15 mg), dulaglutide (1.5 mg) or placebo. Serum lipoprotein profile, apolipoprotein (apo) A-I, B and C-III and preheparin lipoprotein lipase (LPL) were measured at baseline and at 4, 12 and 26 weeks. Lipoprotein particle profile by nuclear magnetic resonance was assessed at baseline and 26 weeks. The lipoprotein insulin resistance (LPIR) score was calculated. Results: At 26 weeks, tirzepatide dose-dependently decreased apoB and apoC-III levels, and increased serum preheparin LPL compared with placebo. Tirzepatide 10 and 15 mg decreased large triglyceride-rich lipoprotein particles (TRLP), small lowdensity lipoprotein particles (LDLP) and LPIR score compared with both placebo and dulaglutide. Treatment with dulaglutide also reduced apoB and apoC-III levels but had no effect on either serum LPL or large TRLP, small LDLP and LPIR score. The number of total LDLP was also decreased with tirzepatide 10 and 15 mg compared with placebo. A greater reduction in apoC-III with tirzepatide was observed in patients with high compared with normal baseline triglycerides. At 26 weeks, change in apoC-III, but not body weight, was the best predictor of changes in triglycerides with tirzepatide, explaining up to 22.9% of their variability.

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“…In humans, GIP induces cytokine expression, lipolysis and insulin resistance in adipocytes, 57 and hGIP(3-30) inhibits GIP-induced increases in abdominal adipose tissue blood flow and decreases adipose tissue triacylglyceride uptake. 58,59 Furthermore, knowledge that highly effective bariatric weight loss surgeries are, in part, linked to surgical removal of GIP-secreting K cells and compromised GIP secretion 13,14 strongly suggests translatable benefits of GIPR antagonists for human obesity. Notably, the dose of GIPR antagonists employed for the current study is well beyond normal circulating levels of GIP, 60 implying that such regimens would effectively annul the biological actions of endogenously released GIP.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonists in Rodent Pancreatic Beta Cells and Mice

et al. 2019

Clin Med Insights Endocrinol Diabetes

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Hypersecretion and alterations in the biological activity of the incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), have been postulated as contributing factors in the development of obesity-related diabetes. However, recent studies also point to weight-reducing effects of GIP receptor activation. Therefore, generating precise experimental tools, such as specific and effective GIP receptor (GIPR) antagonists, is of key significance to better understand GIP physiology. Thus, the primary aim of the current study was to uncover improved GIPR antagonists for use in rodent studies, using human and mouse GIP sequences with N- and C-terminal deletions. Initial in vitro studies revealed that the GIPR agonists, human (h) GIP(1-42), hGIP(1-30) and mouse (m) GIP(1-30), stimulated ( P < 0.01 to P < 0.001) insulin secretion from rat BRIN-BD11 cells. Analysis of insulin secretory effects of the N- and C-terminally cleaved GIP peptides, including hGIP(3-30), mGIP(3-30), h(Pro3)GIP(3-30), hGIP(5-30), hGIP(3-42) and hGIP(5-42), revealed that these peptides did not modulate insulin secretion. More pertinently, only hGIP(3-30), mGIP(3-30) and h(Pro3)GIP(3-30) were able to significantly ( P < 0.01 to P < 0.001) inhibit hGIP(1-42)-stimulated insulin secretion. The human-derived GIPR agonist sequences, hGIP(1-42) and hGIP(1-30), reduced ( P < 0.05) glucose levels in mice following conjoint injection with glucose, but mGIP(1-30) was ineffective. None of the N- and C-terminally cleaved GIP peptides affected glucose homeostasis when injected alone with glucose. However, hGIP(5-30) and mGIP(3-30) significantly ( P < 0.05 to P < 0.01) impaired the glucose-lowering action of hGIP(1-42). Further evaluation of these most effective sequences demonstrated that mGIP(3-30), but not hGIP(5-30), effectively prevented GIP-induced elevations of plasma insulin concentrations. These data highlight, for the first time, that mGIP(3-30) represents an effective molecule to inhibit GIPR activity in mice.

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GIP-induced vasodilation in human adipose tissue involves capillary recruitment

Cited by 25 publications

References 37 publications

Gut–adipose tissue crosstalk: A bridge to novel therapeutic targets in metabolic syndrome?

Gut–adipose tissue crosstalk: A bridge to novel therapeutic targets in metabolic syndrome?

The dual glucose‐dependent insulinotropic peptide and glucagon‐like peptide‐1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes

Characterisation of Glucose-Dependent Insulinotropic Polypeptide Receptor Antagonists in Rodent Pancreatic Beta Cells and Mice

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