scholarly journals Effects of Type 2 Diabetes on Insulin Secretion, Insulin Action, Glucose Effectiveness, and Postprandial Glucose Metabolism

Diabetes Care ◽  
2009 ◽  
Vol 32 (5) ◽  
pp. 866-872 ◽  
Author(s):  
A. Basu ◽  
C. Dalla Man ◽  
R. Basu ◽  
G. Toffolo ◽  
C. Cobelli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Insulin Action ◽  
Postprandial Glucose ◽  
Glucose Effectiveness

scholarly journals Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

2022 ◽  
Author(s):  
Marta Garaulet ◽  
Jesus Lopez-Minguez ◽  
Hassan S Dashti ◽  
Céline Vetter ◽  
Antonio Miguel Hernández-Martínez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Elevated Concentration ◽  
Endogenous Melatonin

<strong>Objective: </strong>We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (<i>MTNR1B</i>).<strong> </strong> <p><strong>Research Design and Methods:</strong> In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant <strong>(n=845) </strong>underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime <strong>(“early dinner-timing”)</strong>, and a late condition scheduled 1 hour prior to habitual bedtime <strong>(“late dinner-timing”)</strong>, simulating an early and a late dinner timing, respectively.<strong> </strong>Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between <strong>early and late dinner-timing.</strong><strong></strong></p> <p><strong>Results:</strong> <strong>Melatonin serum levels were </strong>3.5-fold <strong>higher in the late <i>vs. </i>early condition, with late dinner-timing resulting in </strong>6.7% <strong>lower insulin</strong> <strong>area-under-the-curve (AUC) and </strong>8.3%<strong> higher glucose</strong> <strong>AUC. In the late condition<i> MTNR1B</i> G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in </strong>β-cell <strong>function (<i>P<sub>int</sub></i><sub> </sub>AUCgluc=0.009, <i>P<sub>int</sub></i><sub> </sub>CIR=0.022, <i>P<sub>int </sub></i>DI=0.018).</strong></p> <p><strong>Conclusions:</strong> <strong>Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in <i>MTNR1B</i> G-risk-allele carriers<i>, </i>attributable to insulin secretion defects.</strong></p>

scholarly journals The impact of dietary protein restriction on insulin secretion and action

1999 ◽  
Vol 58 (3) ◽  
pp. 647-653 ◽  
Author(s):  
Mark J. Holness
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Action ◽  
Synergistic Effects ◽  
Protein Restriction ◽  
Dependent Diabetes Mellitus ◽  
Organ Systems ◽  
The Impact

The goal of this review is to develop the hypothesis, and review the evidence, that protein restriction, through synergistic effects on multiple organ systems predisposes to loss of normal regulation of fuel homeostasis that plays the central role in the development of type 2 (non-insulin-dependent) diabetes mellitus. The ability of insulin to regulate glucose production and disposal varies between individuals. These differences, together with the various compensatory mechanisms that are invoked to attempt to normalize fuel homeostasis, are of fundamental importance in the development and clinical course of type 2 diabetes mellitus. Protein deprivation impacts on both insulin secretion and insulin action. These effects may persist even when a diet containing adequate protein is presented subsequently. Data are presented that suggest that protein restriction results in an impaired ability of pancreatic β-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. This persistent impairment of insulin secretion resulting from protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of a diabetogenic challenge. This inability to maintain the degree of compensatory hyperinsulinaemia necessary to prevent loss of glucose tolerance may have relevance to the increased incidence of diabetes on changing from a nutritionally-poor diet to a Western diet, and to the hypothesis that some cases of type 2 diabetes in adulthood may be related to poor early nutrition.

scholarly journals Metabolic and functional specialisations of the pancreatic beta cell: gene disallowance, mitochondrial metabolism and intercellular connectivity

Diabetologia ◽  
2020 ◽  
Vol 63 (10) ◽  
pp. 1990-1998 ◽  
Author(s):  
Guy A. Rutter ◽  
Eleni Georgiadou ◽  
Aida Martinez-Sanchez ◽  
Timothy J. Pullen
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Beta Cell ◽  
Beta Cells ◽  
Mitochondrial Metabolism ◽  
Monocarboxylate Transporter ◽  
Genome Wide Association Studies ◽  
Monocarboxylate Transporter 1

Abstract All forms of diabetes mellitus involve the loss or dysfunction of pancreatic beta cells, with the former predominating in type 1 diabetes and the latter in type 2 diabetes. Deeper understanding of the coupling mechanisms that link glucose metabolism in these cells to the control of insulin secretion is therefore likely to be essential to develop new therapies. Beta cells display a remarkable metabolic specialisation, expressing high levels of metabolic sensing enzymes, including the glucose transporter GLUT2 (encoded by SLC2A2) and glucokinase (encoded by GCK). Genetic evidence flowing from both monogenic forms of diabetes and genome-wide association studies for the more common type 2 diabetes, supports the importance for normal glucose-stimulated insulin secretion of metabolic signalling via altered ATP generation, while also highlighting unsuspected roles for Zn2+ storage, intracellular lipid transfer and other processes. Intriguingly, genes involved in non-oxidative metabolic fates of the sugar, such as those for lactate dehydrogenase (LDHA) and monocarboxylate transporter-1 ([MCT-1] SLC16A1), as well as the acyl-CoA thioesterase (ACOT7) and others, are selectively repressed (‘disallowed’) in beta cells. Furthermore, mutations in genes critical for mitochondrial oxidative metabolism, such as TRL-CAG1–7 encoding tRNALeu, are linked to maternally inherited forms of diabetes. Correspondingly, impaired Ca2+ uptake into mitochondria, or collapse of a normally interconnected mitochondrial network, are associated with defective insulin secretion. Here, we suggest that altered mitochondrial metabolism may also impair beta cell–beta cell communication. Thus, we argue that defective oxidative glucose metabolism is central to beta cell failure in diabetes, acting both at the level of single beta cells and potentially across the whole islet to impair insulin secretion.

Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion

2015 ◽  
Vol 56 (1) ◽  
pp. 237-246 ◽  
Author(s):  
Emi Arimura ◽  
Wijang Pralampita Pulong ◽  
Ancah Caesarina Novi Marchianti ◽  
Miwa Nakakuma ◽  
Masaharu Abe ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Animal Model ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
High Protein ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate

scholarly journals Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without Type 2 diabetes

2014 ◽  
Vol 306 (4) ◽  
pp. G301-G309 ◽  
Author(s):  
Sara Chowdhury ◽  
Dominic N. Reeds ◽  
Dan L. Crimmins ◽  
Bruce W. Patterson ◽  
Erin Laciny ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Gastric Emptying ◽  
Postprandial Glucose ◽  
Nerve Fibers ◽  
Intense Staining ◽  
Glucose Levels ◽  
Healthy Humans ◽  
Glucagon Like Peptide 1

Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10–14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol·kg−1·min−1 was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions.

Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

2015 ◽  
Vol 308 (6) ◽  
pp. E535-E544 ◽  
Author(s):  
Christoffer Martinussen ◽  
Kirstine N. Bojsen-Møller ◽  
Carsten Dirksen ◽  
Siv H. Jacobsen ◽  
Nils B. Jørgensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Glucose Effectiveness ◽  
Β Cell Function ◽  
First Phase Insulin Secretion

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

23-OR: The Effect of 14-Day Atorvastatin Treatment on Postprandial Glucose Metabolism in Healthy Males—A Link to Why Statin Therapy Increases the Risk of Type 2 Diabetes?

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 23-OR
Author(s):  
MARTIN L. THOMASEN ◽  
DAVID P. SONNE ◽  
MARTIN L. KÅRHUS ◽  
ANDREAS BRØNDEN ◽  
BART STAELS ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Statin Therapy ◽  
Postprandial Glucose ◽  
Atorvastatin Treatment ◽  
Healthy Males

scholarly journals Exocytosis mechanisms underlying insulin release and glucose uptake: conserved roles for Munc18c and syntaxin 4

2010 ◽  
Vol 298 (3) ◽  
pp. R517-R531 ◽  
Author(s):  
Jenna L. Jewell ◽  
Eunjin Oh ◽  
Debbie C. Thurmond
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Uptake ◽  
Pancreatic Beta Cells ◽  
Insulin Action ◽  
Molecular Mechanisms ◽  
Receptor Protein ◽  
Peripheral Tissues ◽  
Syntaxin 4

Type 2 diabetes has been coined “a two-hit disease,” as it involves specific defects of glucose-stimulated insulin secretion from the pancreatic beta cells in addition to defects in peripheral tissue insulin action required for glucose uptake. Both of these processes, insulin secretion and glucose uptake, are mediated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein core complexes composed of syntaxin, SNAP-23/25, and VAMP proteins. The SNARE core complex is regulated by the Sec1/Munc18 (SM) family of proteins, which selectively bind to their cognate syntaxin isoforms with high affinity. The process of insulin secretion uses multiple Munc18-syntaxin isoform pairs, whereas insulin action in the peripheral tissues appears to use only the Munc18c-syntaxin 4 pair. Importantly, recent reports have linked obesity and Type 2 diabetes in humans with changes in protein levels and single nucleotide polymorphisms (SNPs) of Munc18 and syntaxin isoforms relevant to these exocytotic processes, although the molecular mechanisms underlying the observed phenotypes remain incomplete ( 5 , 104 , 144 ). Given the conservation of these proteins in two seemingly disparate processes and the need to design and implement novel and more effective clinical interventions, it will be vitally important to delineate the mechanisms governing these conserved SNARE-mediated exocytosis events. Thus, we provide here an up-to-date historical review of advancements in defining the roles and molecular mechanisms of Munc18-syntaxin complexes in the pathophysiology of Type 2 diabetes.

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