scholarly journals Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 376
Author(s):  
Christian Göbl ◽  
Micaela Morettini ◽  
Benedetta Salvatori ◽  
Wathik Alsalim ◽  
Hana Kahleova ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Area Under The Curve ◽  
Glucagon Secretion ◽  
Plasma Glucagon ◽  
Food Ingestion ◽  
Mixed Meal ◽  
C Peptide ◽  
Significant Relationships ◽  
Basal Insulin Secretion ◽  
Secretion Inhibition

Background: glucagon secretion and inhibition should be mainly determined by glucose and insulin levels, but the relative relevance of each factor is not clarified, especially following ingestion of different macronutrients. We aimed to investigate the associations between plasma glucagon, glucose, and insulin after ingestion of single macronutrients or mixed-meal. Methods: thirty-six participants underwent four metabolic tests, based on administration of glucose, protein, fat, or mixed-meal. Glucagon, glucose, insulin, and C-peptide were measured at fasting and for 300 min following food ingestion. We analyzed relationships between time samples of glucagon, glucose, and insulin in each individual, as well as between suprabasal area-under-the-curve of the same variables (ΔAUCGLUCA, ΔAUCGLU, ΔAUCINS) over the whole participants’ cohort. Results: in individuals, time samples of glucagon and glucose were related in only 26 cases (18 direct, 8 inverse relationships), whereas relationship with insulin was more frequent (60 and 5, p < 0.0001). The frequency of significant relationships was different among tests, especially for direct relationships (p ≤ 0.006). In the whole cohort, ΔAUCGLUCA was weakly related to ΔAUCGLU (p ≤ 0.02), but not to ΔAUCINS, though basal insulin secretion emerged as possible covariate. Conclusions: glucose and insulin are not general and exclusive determinants of glucagon secretion/inhibition after mixed-meal or macronutrients ingestion.

Oral sensory stimulation improves glucose tolerance in humans: effects on insulin, C-peptide, and glucagon

1996 ◽  
Vol 270 (6) ◽  
pp. R1371-R1379 ◽  
Author(s):  
K. L. Teff ◽  
K. Engelman
Keyword(s):  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Area Under The Curve ◽  
Sensory Stimulation ◽  
Sampling Period ◽  
Intragastric Administration ◽  
Plasma Glucagon ◽  
C Peptide ◽  
Oral Sensory ◽  
Normal Glucose

In animals, bypassing the oropharyngeal receptors by intragastric administration of glucose results in glucose intolerance. To determine whether the absence of oral sensory stimulation alters glucose tolerance in humans, we monitored plasma levels of glucose and hormones after intragastric administration of glucose, with and without subjects tasting food. Plasma glucose area under the curve (AUC) was significantly lower after oral sensory stimulation (3,433 +/- 783 vs. 5,643 +/- 1,397 mg.dl-1. 195 min-1; P < 0.03; n = 8). Insulin and C-peptide AUCs were higher during the first one-half of the sampling period (insulin, 5,771 +/- 910 vs. 4,295 +/- 712 microU. ml-1.75 min-1; P < 0.05; C-peptide, 86 +/- 10 vs. 66 +/- 9 ng.ml-1. 75 min-1; P < 0.03) and lower during the second one-half of the sampling period compared with the control condition (1,010 +/- 233 vs. 2,106 microU.ml-1. 120 min-1; P < 0.025; 31 +/- 8 vs. 56 +/- 18 ng.ml-1. 120 min-1; P < 0.05; insulin and C-peptide, respectively). Oral sensory stimulation markedly increased plasma glucagon compared with the control condition (1,258 +/- 621 vs. -2,181 +/- 522 pg.ml-1. 195 min-1; P < 0.002). These data provide evidence in humans that oral sensory stimulation influences glucose metabolism and suggest that the mechanisms elicited by this cephalic stimulation are necessary for normal glucose homeostasis.

scholarly journals Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin

2016 ◽  
Vol 101 (4) ◽  
pp. 1798-1806 ◽  
Author(s):  
Anna Vanderheiden ◽  
Lindsay B. Harrison ◽  
Jeremy T. Warshauer ◽  
Beverley Adams-Huet ◽  
Xilong Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Treatment ◽  
Glycosylated Hemoglobin ◽  
Challenge Test ◽  
Glucagon Secretion ◽  
Mechanisms Of Action ◽  
High Dose ◽  
C Peptide

Abstract Context: The mechanisms of action of incretin mimetics in patients with long-standing type 2 diabetes (T2D) and high insulin requirements have not been studied. Objective: To evaluate changes in β-cell function, glucagon secretion, and fat distribution after addition of liraglutide to high-dose insulin. Design: A single-center, randomized, double-blind, placebo-controlled trial. Setting: University of Texas Southwestern and Parkland Memorial Hospital clinics. Patients: Seventy-one patients with long-standing (median, 17 years) T2D requiring high-dose insulin treatment (&gt;1.5 U/kg/d; average, 2.2 ± 0.9 U/kg/d). Intervention: Patients were randomized to liraglutide 1.8 mg/d or matching placebo for 6 months. Main Outcome Measures: We measured changes in insulin and glucagon secretion using a 4-hour mixed-meal challenge test. Magnetic resonance-based techniques were used to estimate sc and visceral fat in the abdomen and ectopic fat in the liver and pancreas. Results: Glycosylated hemoglobin improved significantly with liraglutide treatment, with an end-of-trial estimated treatment difference between groups of −0.9% (95% confidence interval, −1.5, −0.4%) (P = .002). Insulin secretion improved in the liraglutide group vs placebo, as measured by the area under the curve of C-peptide (P = .002) and the area under the curves ratio of C-peptide to glucose (P = .003). Insulin sensitivity (Matsuda index) and glucagon secretion did not change significantly between groups. Liver fat and sc fat decreased in the liraglutide group vs placebo (P = .0006 and P = .01, respectively), whereas neither visceral nor pancreatic fat changed significantly. Conclusions: Treatment with liraglutide significantly improved insulin secretion, even in patients with long-standing T2D requiring high-dose insulin treatment. Liraglutide also decreased liver and sc fat, but it did not alter glucagon secretion.

Effects of galanin and calcitonin gene-related peptide on insulin and glucagon secretion in man

1990 ◽  
Vol 123 (6) ◽  
pp. 591-597 ◽  
Author(s):  
Bo Ahrén
Keyword(s):  
Insulin Secretion ◽  
Plasma Insulin ◽  
Glucagon Secretion ◽  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
C Peptide ◽  
Related Peptide ◽  
Insulin And Glucagon Secretion ◽  
Calcitonin Gene ◽  
Human Volunteers

Abstract. To study the influence of the pancreatic neuropeptides, galanin and calcitonin gene-related peptide, on insulin and glucagon secretion in man, synthetic porcine galanin (80 pmol·kg−1·min−1; N=6) or synthetic human calcitonin gen-related peptide (10 pmol·kg−1·min−1; N = 5) was infused intravenously in human volunteers. Following 5 min of infusion, arginine (5 g bolus + 10 mg·kg−1·min−1) was given. Galanin did not affect basal or arginine-stimulated insulin secretion judged from determinations of plasma insulin and C-peptide. Similarly, galanin did not affect arginine-stimulated glucagon secretion. Calcitonin gene-related peptide did not affect basal or arginine-stimulated insulin or glucagon secretion. However, calcitonin gene-related peptide slightly potentiated the arginine-induced hyperglycemia (p<0.01). Thus, in man, galanin has no influence on insulin or glucagon secretion when infused at 80 pmol·kg−1·min−1, whereas CGRP at 10 pmol·kg−1·min−1 induces slight hyperglycemia.

scholarly journals Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test

2021 ◽  
Vol 12 ◽  
Author(s):  
Micaela Morettini ◽  
Laura Burattini ◽  
Christian Göbl ◽  
Giovanni Pacini ◽  
Bo Ahrén ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Insulin Secretion ◽  
Clinical Practice ◽  
Glucose Tolerance Test ◽  
Glucagon Secretion ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
C Peptide ◽  
Proposed Model

Glucagon is secreted from the pancreatic alpha cells and plays an important role in the maintenance of glucose homeostasis, by interacting with insulin. The plasma glucose levels determine whether glucagon secretion or insulin secretion is activated or inhibited. Despite its relevance, some aspects of glucagon secretion and kinetics remain unclear. To gain insight into this, we aimed to develop a mathematical model of the glucagon kinetics during an oral glucose tolerance test, which is sufficiently simple to be used in the clinical practice. The proposed model included two first-order differential equations -one describing glucagon and the other describing C-peptide in a compartment remote from plasma - and yielded a parameter of possible clinical relevance (i.e., SGLUCA(t), glucagon-inhibition sensitivity to glucose-induced insulin secretion). Model was validated on mean glucagon data derived from the scientific literature, yielding values for SGLUCA(t) ranging from -15.03 to 2.75 (ng of glucagon·nmol of C-peptide-1). A further validation on a total of 100 virtual subjects provided reliable results (mean residuals between -1.5 and 1.5 ng·L-1) and a negative significant linear correlation (r = -0.74, p &lt; 0.0001, 95% CI: -0.82 – -0.64) between SGLUCA(t) and the ratio between the areas under the curve of suprabasal remote C-peptide and glucagon. Model reliability was also proven by the ability to capture different patterns in glucagon kinetics. In conclusion, the proposed model reliably reproduces glucagon kinetics and is characterized by sufficient simplicity to be possibly used in the clinical practice, for the estimation in the single individual of some glucagon-related parameters.

Altered insulin and glucagon secretion in perfused ethionine-treated rat pancreases

1982 ◽  
Vol 243 (6) ◽  
pp. E505-E511
Author(s):  
K. V. Axen ◽  
F. X. Pi-Sunyer
Keyword(s):  
Insulin Secretion ◽  
Glucagon Secretion ◽  
Gastric Inhibitory Polypeptide ◽  
Oral Glucose ◽  
Secretory Function ◽  
Acinar Structure ◽  
Basal Insulin Secretion ◽  
Pathogenic Action ◽  
Insulin Responses

The endocrine secretory function of rat pancreases in which pancreatitis had been induced by feeding rats a 0.5% ethionine diet was investigated. Despite loss of 50% of exocrine tissue and widespread destruction of acinar structure, pancreatic insulin and glucagon contents and 4-h fasting plasma insulin levels in vivo did not differ significantly from those of food-restricted, weight-matched controls. Plasma glucose concentrations (fasting and after oral glucose) were significantly lower than control. In isolated, perfused ethionine-treated pancreases secretin failed to stimulate insulin secretion, whereas basal insulin secretion and insulin responses to glucose, arginine, gastric inhibitory polypeptide, vasoactive intestinal peptide (VIP), and somatostatin were similar to those of controls. Basal glucagon secretion was elevated in ethionine-treated pancreases, and glucagon outputs in response to arginine, VIP, and somatostatin showed a consistent trend toward higher levels than those of controls. These findings demonstrate that ethionine-induced pancreatitis selectively impairs islet secretory function. These effects may be due to damage to islet cell membranes by exocrine enzymes and/or a direct pathogenic action of ethionine on the islets.

scholarly journals A model of GLP-1 action on insulin secretion in nondiabetic subjects

2010 ◽  
Vol 298 (6) ◽  
pp. E1115-E1121 ◽  
Author(s):  
Chiara Dalla Man ◽  
Francesco Micheletto ◽  
Airani Sathananthan ◽  
Robert A. Rizza ◽  
Adrian Vella ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Basal Insulin ◽  
Mechanistic Model ◽  
Rate Of Change ◽  
Percentage Increase ◽  
Common Assumption ◽  
C Peptide ◽  
Hyperglycemic Clamp ◽  
Basal Insulin Secretion ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1)-based therapies for diabetes have aroused interest because of their effects on insulin secretion and glycemic control. However, a mechanistic model enabling quantitation of pancreatic response to GLP-1 has never been developed. To develop such a model we studied 88 healthy individuals (age 26.3 ± 0.6 yr, BMI 24.9 ± 0.4 kg/m2) by use of a hyperglycemic clamp. A variable infusion maintained glucose concentrations at 150 mg/dl for 240 min. At 120 min, an intravenous infusion of GLP-1 was started (0.75 pmol·kg−1·min−1 from 120–180 min, 1.5 pmol·kg−1·min−1 from 181–240 min). Consequently, plasma C-peptide concentration rose from 1,852.0 ± 62.8 pmol/l at 120 min to 4,272.2 ± 176.4 pmol/l at 180 min and to 6,995.8 ± 323.5 pmol/l at 240 min. Four models of GLP-1 action on insulin secretion were considered. All models share the common assumption that insulin secretion is made up of two components, one proportional to glucose rate of change through dynamic responsivity, Φd, and one proportional to glucose through static responsivity, Φs, but differing by modality of GLP-1 control. The model that best fit C-peptide data assumes that above-basal insulin secretion depends linearly on GLP-1 concentration and its rate of change. An index (Π) measuring the percentage increase of secretion due to GLP-1 is derived. Before GLP-1 infusion, Φd = 245.7 ± 15.6 10−9 and Φs = 25.2 ± 1.4 10−9 min−1. Under GLP-1 stimulus, Π = 12.6 ± 0.71% per pmol/l, meaning that an increase of 5 pmol/l in peripheral GLP-1 concentrations induces an ∼60% increase in over-basal insulin secretion.

scholarly journals Effect of Glucagon-Like Peptide-1 on α- and β-Cell Function in C-Peptide-Negative Type 1 Diabetic Patients

2010 ◽  
Vol 24 (4) ◽  
pp. 875-875
Author(s):  
Urd Kielgast ◽  
Meena Asmar ◽  
Sten Madsbad ◽  
Jens J. Holst
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Diabetic Patients ◽  
Β Cell ◽  
C Peptide ◽  
Endogenous Insulin Secretion ◽  
Endogenous Insulin ◽  
Type 1 Diabetic Patients

Abstract Context: The mechanism by which glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion is uncertain, and it is not determined whether endogenous insulin is a necessary factor for this effect. Objective: Our objective was to characterize the α- and β-cell responses to GLP-1 in type 1 diabetic patients without residual β-cell function. Methods: Nine type 1 diabetic patients, classified as C-peptide negative by a glucagon test, were clamped at plasma glucose of 20 mmol/liter for 90 min with arginine infusion at time 45 min and concomitant infusion of GLP-1 (1.2 pmol/kg · min) or saline. Results: Infusion with GLP-1 increased C-peptide concentration just above the detection limit of 33 pmol/liter in one patient, but C-peptide remained immeasurable in all other patients. In the eight remaining patients, total area under the curve of glucagon was significantly decreased with GLP-1 compared with saline: 485 ± 72 vs. 760 ± 97 pmol/liter · min (P &lt; 0.001). In addition, GLP-1 decreased the arginine-stimulated glucagon release (incremental AUC of 103 ± 21 and 137 ± 16 pmol/liter · min, with GLP-1 and saline, respectively, P &lt; 0.05). Conclusions: In type 1 diabetic patients without endogenous insulin secretion, GLP-1 decreases the glucagon secretion as well as the arginine-induced glucagon response during hyperglycemia. GLP-1 induced endogenous insulin secretion in one of nine type 1 diabetic patients previously classified as being without endogenous insulin secretion.

Adrenergic modulation of pancreatic glucagon and insulin secretion in sheep

1988 ◽  
Vol 254 (3) ◽  
pp. R518-R523 ◽  
Author(s):  
S. Oda ◽  
A. Hagino ◽  
A. Ohneda ◽  
Y. Sasaki ◽  
T. Tsuda
Keyword(s):  
Insulin Secretion ◽  
Intravenous Infusion ◽  
Glucagon Secretion ◽  
Receptor Activation ◽  
Plasma Glucagon ◽  
Epinephrine Infusion ◽  
Plasma Insulin Concentration ◽  
Pancreatic Glucagon ◽  
Adrenergic Modulation ◽  
Glucagon And Insulin

The effect of intravenous infusion of epinephrine, either alone or together with various doses of phentolamine or propranolol, on the secretion of both glucagon and insulin was determined in six sheep. Intravenous infusion of epinephrine alone caused increases in plasma glucagon and glucose concentrations and produced a slight but significant decrease in plasma insulin concentration. The concomitant infusion of propranolol and epinephrine augmented glucagon release and inhibited insulin secretion. Combined propranolol plus epinephrine infusion also caused a marked hyperglycemia. The concomitant infusion of phentolamine and epinephrine produced slight inhibition of glucagon secretion and markedly promoted insulin secretion. Epinephrine-induced hyperglycemia was eliminated by phentolamine infusion. The effects of isoproterenol infusion on plasma glucagon, insulin, and glucose concentrations were similar to that caused by the concomitant infusion of phentolamine and epinephrine. The effects of isoproterenol were abolished by the infusion of propranolol. It is concluded that an alpha-receptor mechanism is the most important component of adrenergic modulation of pancreatic glucagon secretion, whereas beta-receptor activation stimulates and alpha-receptor activation inhibits insulin secretion in sheep.

Hypoglycemia owing to inappropriate glucagon secretion treated with a continuous subcutaneous glucagon infusion system

1990 ◽  
Vol 122 (3) ◽  
pp. 319-322 ◽  
Author(s):  
Roger Abs ◽  
Louis Verbist ◽  
Marleen Moeremans ◽  
Pierre Blockx ◽  
Ivo De Leeuw ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Case Report ◽  
Female Patient ◽  
Glucose Level ◽  
Glucagon Secretion ◽  
Glucagon Release ◽  
Plasma Glucagon ◽  
Arginine Test ◽  
Fasting Plasma ◽  
Infusion System

Abstract A selective glucagon deficiency was documented in a 36-year-old female patient suffering from severe hypoglycemic attacks. The extremely low fasting plasma glucagon levels could not be stimulated by hypoglycemia. The increase in plasma glucagon during stimulation with arginine did not prevent hypoglycemia provoked by the simultaneous insulin secretion. Treatment consisting of a continuous sc glucagon infusion system resulted in correction of both postabsorptive and postprandial hypoglycemia. Further lowering of the glucose level during an arginine test could be the hallmark of this hypoglycemic syndrome characterized by an inappropriate glucagon secretion. This case report would indicate that epinephrine cannot prevent hypoglycemia when glucagon release is completely deficient.

scholarly journals Baseline Assessment of Circulating microRNAs Near Diagnosis of Type 1 Diabetes Predicts Future Stimulated Insulin Secretion

2020 ◽  
Author(s):  
Ada Admin ◽  
Isaac Snowhite ◽  
Ricardo Pastori ◽  
Jay Sosenko ◽  
Shari Messinger Cayetano ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Type 1 Diabetes ◽  
Insulin Secretion ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Tolerance Test ◽  
Circulating Micrornas ◽  
C Peptide ◽  
Impaired Insulin

Type 1 diabetes is an autoimmune disease resulting in severely impaired insulin secretion. We investigated whether circulating microRNAs (miRNAs) are associated with residual insulin secretion at diagnosis and predict the severity of its future decline. We studied 53 newly diagnosed subjects enrolled in placebo groups of TrialNet clinical trials. We measured serum levels of 2,083 miRNAs using RNAseq technology, in fasting samples from the baseline visit (<100 days from diagnosis), during which residual insulin secretion was measured with a mixed meal tolerance test (MMTT). Area under the curve (AUC) C-peptide and peak C-peptide were stratified by quartiles of expression of 31 miRNAs. After adjustment for baseline C-peptide, age, BMI and sex, baseline levels of miR-3187-3p, miR-4302, and the miRNA combination of miR-3187-3p/miR-103a-3p predicted differences in MMTT C-peptide AUC/peak levels at the 12-month visit; the combination miR-3187-3p/miR-4723-5p predicted proportions of subjects above/below the 200 pmol/L clinical trial eligibility threshold at the 12-month visit. Thus, miRNA assessment at baseline identifies associations with C-peptide and stratifies subjects for future severity of C-peptide loss after 1 year. We suggest that miRNAs may be useful in predicting future C-peptide decline for improved subject stratification in clinical trials.

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