Gut hormones and diabetes mellitus

Creutzfeldt, W.; Nauck, Michael A.

doi:10.1002/dmr.5610080206

Cited by 183 publications

(119 citation statements)

References 267 publications

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“…Since insulin secretion is increased by incretins after oral glucose ingestion, the possibility that these hormones affect beta cell secretion must be taken into consideration [37].…”

Section: Discussionmentioning

confidence: 99%

Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes: a report from the GAMI study

et al. 2005

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Aims/hypothesis: Patients with acute myocardial infarction (AMI) but without previously known type 2 diabetes have a high prevalence of undiagnosed IGT and type 2 diabetes. Such perturbations have dismal prognostic implications. The aim of this study was to characterise AMI patients in terms of insulin resistance and beta cell function. Methods: A total of 168 consecutive AMI patients were classified by means of an OGTT before hospital discharge as having NGT, IGTor type 2 diabetes. The homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Beta cell responsiveness was quantified as insulinogenic index (IGI) at 30 min (ΔI 30 /ΔG 30 (r=−0.218, p=0.010) and to the area under the curve for glucose (r=−0.475, p<0.001). Conclusions/interpretation: Glucose abnormalities are very common in patients with AMI but without previously known type 2 diabetes. To a significant extent, this seems to be related to impaired beta cell function and implies that dysglycaemia immediately after an infarction is not a stress epiphenomenon but reflects stable disturbances of glucose regulation preceding the AMI. Early beta cell dysfunction may have important pathophysiological implications and may serve as a future target for treatment strategies.

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“…Since insulin secretion is increased by incretins after oral glucose ingestion, the possibility that these hormones affect beta cell secretion must be taken into consideration [37].…”

Section: Discussionmentioning

confidence: 99%

Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes: a report from the GAMI study

et al. 2005

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“…Increased somatostatin secretion in response to GLP-1 has been shown in both perfused rat pancreas (Schmid et al, 1990) and isolated islets (Fehmann et al, 1995). GIP, in contrast, actually increases glucagon secretion in healthy subjects under normoglycemic conditions (Meier et al, 2003) while having no effect in T2DM (Creutzfeldt and Nauck, 1992). The inference is that GIP is not glucagonotropic under hyperglycemic conditions.…”

Section: Effects On Glucagon Secretion Are They Direct or Indirect?mentioning

confidence: 95%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

584

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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“…This effect is mediated by the secretion of peptide hormones from the gut, which stimulate insulin secretion [2,3]. The two known incretin hormones are gastric inhibitory polypeptide (GIP; also referred to as glucose-dependent insulinotropic polypeptide) and glucagon-like peptide 1 (GLP-1) [4,5].…”

Section: Introductionmentioning

confidence: 99%

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

et al. 2005

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Aims/hypothesis: The insulinotropic effect of gastric inhibitory polypeptide (GIP) is reduced in patients with type 2 diabetes and around 50% of their first-degree relatives under hyperglycaemic conditions. It is unknown whether this is a result of a specific defect in GIP action or of a general reduction in beta cell function. Moreover, impaired secretion of glucagon-like peptide 1 (GLP-1) has been described in patients with type 2 diabetes. Therefore, we studied the insulinotropic effect of GIP in women with previous gestational diabetes (pGDM) under euglycaemic fasting conditions and during a hyperglycaemic clamp experiment. The secretion of GIP and GLP-1 was assessed following oral glucose ingestion. Materials and methods:On separate occasions we performed an OGTT and administered an i.v. bolus of 20 pmol GIP/kg body weight in 20 women with pGDM and 20 control women. An additional hyperglycaemic clamp experiment (140 mg/dl [7.8 mmol/l] over 120 min) with i.v. infusion of GIP (2 pmol kg −1 min −1 ; 30-90 min) was performed in 14 women in each group. Capillary and venous blood samples were drawn for the measurement of glucose (glucose oxidase), insulin, C-peptide, GIP and GLP-1 (specific immunoassays). Indices of insulin sensitivity and beta cell function were calculated. Statistical analyses were carried out using repeated measures ANOVA. Results: Following oral glucose ingestion, plasma glucose, insulin and C-peptide concentrations increased to higher levels in the women with pGDM than in the control women (p<0.05). The women with pGDM were characterised by a higher degree of insulin resistance than the control women (p=0.007 for the Matsuda index), but showed no overt defects in glucosestimulated insulin secretion (p=0.40 for the insulinogenic index following i.v. glucose). The secretion of GLP-1 and GIP was not different between the groups (p=0.87 and p=0.57, respectively). The insulin secretory response to GIP administration was similar in the two groups both after GIP bolus administration and during the hyperglycaemic clamp experiment (p=0.99 and p=0.88, respectively). A hyperbola-like relationship was found between the degree of insulin sensitivity (Matsuda index) and the insulin secretory response to GIP and i.v. glucose administration. Conclusions/interpretation: These results do not support the hypothesis of an early defect in GIP action as a risk factor for subsequent development of diabetes in women with previous gestational diabetes. The inverse relationship between insulin resistance and the insulin secretory response to glucose or GIP suggests that beta cell secretory function in response to different stimuli increases adaptively when insulin sensitivity is diminished.

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Gut hormones and diabetes mellitus

Cited by 183 publications

References 267 publications

Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes: a report from the GAMI study

Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes: a report from the GAMI study

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

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