Aims: Although metformin is widely used for treatment of type 2 diabetes (T2D), its glucose-lowering mechanism remains unclear. Using the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) antagonist exendin(9-39)NH2, we tested the hypothesis that postprandial GLP-1-mediated effects contribute to the glucose-lowering potential of metformin in T2D.
Methods: In a randomized, placebo-controlled, double-blind, crossover study, 15 individuals with T2D (median HbA1c 50 mmol/mol [6.
Aim: Weight bias, stigma and discrimination are pervasive in the health care system and society and may result in biased treatment of people living with obesity (PwO). We aimed to identify perceptions, attitudes and potential barriers that exist between people with obesity and health care professionals (HCPs) in Denmark.
Methods: The ACTION-DK survey was a cross-sectional, non-interventional, descriptive study conducted in Denmark.
Objective: The gut hormone glucose-dependent insulinotropic polypeptide (GIP) is an important regulator of glucose and bone metabolism. In rodents, the naturally occurring GIP variant, GIP(1-30)NH2, has shown similar effects as full-length GIP (GIP(1-42)), but its effects in humans are unsettled. Here, we investigated the actions of GIP(1-30)NH2 compared to GIP(1-42) on glucose and bone metabolism in healthy men and in isolated human pancreatic islets.
View Article and Find Full Text PDFDipeptidyl peptidase 4 (DPP-4) degrades the incretin hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide (GIP). DPP-4 inhibitors improve glycemic control in type 2 diabetes, but the importance of protecting GIP from degradation for their clinical effects is unknown. We included 12 patients with type 2 diabetes (mean ± SD BMI 27 ± 2.
View Article and Find Full Text PDFDiabetes Obes Metab
September 2022
Objective: The insulinotropic effect of exogenous, intravenously infused glucose-dependent insulinotropic polypeptide (GIP) is impaired in patients with type 2 diabetes. We evaluated the effects of endogenous GIP in relation to glucose and bone metabolism in patients with type 2 diabetes using a selective GIP receptor antagonist and hypothesized that the effects of endogenous GIP were preserved.
Design: A randomized, double-blinded, placebo-controlled, crossover study.
Aims: The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes.
View Article and Find Full Text PDFThe glucose-dependent insulinotropic polypeptide (GIP) fragment GIP(3-30)NH is a selective, competitive GIP receptor antagonist, and doses of 800 to 1200 pmol/kg/min inhibit GIP-induced potentiation of glucose-stimulated insulin secretion by >80% in humans. We evaluated the effects of GIP(3-30)NH across a wider dose range in eight healthy men undergoing six separate and randomized 10-mmol/L hyperglycaemic clamps (A-F) with concomitant intravenous infusion of GIP (1.5 pmol/kg/min; A-E) or saline (F).
View Article and Find Full Text PDFThe incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are well known for their insulinotropic effects and they are thought to affect bone homeostasis as mediators in the so-called entero-osseous axis. We examined the contributions of endogenous GIP and GLP-1, respectively, to postprandial bone homeostasis, in healthy subjects in two randomized and double-blind crossover studies. We included healthy men who received either four oral glucose tolerance tests (OGTTs) (n = 18, median age 27 (range 20-70), BMI 27.
View Article and Find Full Text PDFContext: The actions of both endogenous incretin hormones during a meal have not previously been characterized.
Objective: Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility.
Design: Randomized, double-blinded, placebo-controlled, crossover design.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) potentiate glucose-induced insulin secretion and are therefore thought to be responsible for the incretin effect. The magnitude of the incretin effect, defined as the fraction of postprandial insulin secretion stimulated by intestinal factors, has been reported to be up to ∼60% in healthy individuals. In several pathological conditions but especially in patients with type 2 diabetes, the incretin effect is severely reduced or even absent.
View Article and Find Full Text PDFDuring the past four decades derangements in glucose-dependent insulinotropic polypeptide (GIP) biology has been viewed upon as contributing factors to various parts of the pathophysiology type 2 diabetes. This overview outlines and discusses the impaired insulin responses to GIP as well as the effect of GIP on glucagon secretion and the potential involvement of GIP in the obesity and bone disease associated with type 2 diabetes. As outlined in this review, it is unlikely that the impaired insulinotropic effect of GIP occurs as a primary event in the development of type 2 diabetes, but rather develops once the diabetic state is present and beta cells are unable to maintain normoglycemia.
View Article and Find Full Text PDFThe incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted postprandially and contribute importantly to postprandial glucose tolerance. In this study, we assessed the individual and combined contributions of endogenous GIP and GLP-1 to the postprandial changes in glucose and glucoregulatory hormones using the novel GIP receptor antagonist GIP(3-30)NH and the well-established GLP-1 receptor antagonist exendin(9-39)NH During 4-h oral glucose tolerance tests (75 g) combined with an ad libitum meal test, 18 healthy men received on four separate days in randomized, double-blinded order intravenous infusions of A) GIP(3-30)NH (800 pmol/kg/min) plus exendin(9-39)NH (0-20 min: 1,000 pmol/kg/min; 20-240 min: 450 pmol/kg/min), B) GIP(3-30)NH, C) exendin(9-39)NH, and D) saline, respectively. Glucose excursions were significantly higher during A than during B, C, and D, while glucose excursions during B were higher than during C and D.
View Article and Find Full Text PDFUsing a large, population-based survey, we assessed the levels and correlates of human papillomavirus (HPV) awareness among Scandinavian women after introduction of HPV vaccination. In 2011-2012, a random sample of women aged between 18 and 45 years from Denmark, Sweden and Norway received a questionnaire on lifestyle, health and HPV awareness. We included 47 895 women (response rate 60.
View Article and Find Full Text PDFPersistent genital infection with high-risk (HR) human papillomavirus (HPV) is a prerequisite for cervical cancer development. The aim of this study was to identify factors associated with type-specific persistence of HR HPV infections. From a population-based cohort of 40,399 women participating in cervical cancer screening established during 2002-2005, we selected all HR HPV-positive women (N = 7,778).
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