scholarly journals Mechanisms of the Regulation and Dysregulation of Glucagon Secretion

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Arnold N. Onyango
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Blood Glucose Concentration ◽  
Hepatic Glucose Production ◽  
Glucagon Secretion ◽  
Alpha Cell ◽  
High Blood Glucose

Glucagon, a hormone secreted by pancreatic alpha cells, contributes to the maintenance of normal blood glucose concentration by inducing hepatic glucose production in response to declining blood glucose. However, glucagon hypersecretion contributes to the pathogenesis of type 2 diabetes. Moreover, diabetes is associated with relative glucagon undersecretion at low blood glucose and oversecretion at normal and high blood glucose. The mechanisms of such alpha cell dysfunctions are not well understood. This article reviews the genesis of alpha cell dysfunctions during the pathogenesis of type 2 diabetes and after the onset of type 1 and type 2 diabetes. It unravels a signaling pathway that contributes to glucose- or hydrogen peroxide-induced glucagon secretion, whose overstimulation contributes to glucagon dysregulation, partly through oxidative stress and reduced ATP synthesis. The signaling pathway involves phosphatidylinositol-3-kinase, protein kinase B, protein kinase C delta, non-receptor tyrosine kinase Src, and phospholipase C gamma-1. This knowledge will be useful in the design of new antidiabetic agents or regimens.

An Approach to diabetic ketoacidosis in an emergency setting.

2020 ◽  
Vol 15 ◽  
Author(s):  
Dario Pitocco ◽  
Mauro Di Leo ◽  
Linda Tartaglione ◽  
Emanuele Gaetano Rizzo ◽  
Salvatore Caputo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Blood Glucose Concentration ◽  
Diabetic Complication ◽  
Emergency Setting ◽  
Online Activity

Background: Diabetic Ketoacidosis (DKA) is one of the most commonly encountered diabetic complication emergencies. It typically affects people with type 1 diabetes at the onset of the disease. It can also affect people with type 2 diabetes, although this is uncommon. Methods: Research and online content related to diabetes online activity is reviewed. DKA is caused by a relative or absolute deficiency of insulin and elevated levels of counter regulatory hormones. Results: Goals of therapy are to correct dehydration, acidosis and to reverse ketosis, gradually restoring blood glucose concentration to near normal. Conclusion: Furthermore it is essential to monitor potential complications of DKA and if necessary, to treat them and any precipitating events.

scholarly journals Modeling the Effect of Subcutaneous Lixisenatide on Glucoregulatory Endocrine Secretions and Gastric Emptying in Type 2 Diabetes to Simulate the Effect of iGlarLixi Administration Timing on Blood Sugar Profiles

2021 ◽  
pp. 193229682110156
Author(s):  
Thibault Gautier ◽  
Rupesh Silwal ◽  
Aramesh Saremi ◽  
Anders Boss ◽  
Marc D. Breton
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Blood Sugar ◽  
Blood Glucose Concentration ◽  
Fixed Ratio ◽  
Selection Procedure ◽  
Model Complexity ◽  
Evening Meal ◽  
Administration Timing

Background: As type 2 diabetes (T2D) progresses, intensification to combination therapies, such as iGlarLixi (a fixed-ratio GLP-1 RA and basal insulin combination), may be required. Here a simulation study was used to assess the effect of iGlarLixi administration timing (am vs pm) on blood sugar profiles. Methods: Models of lixisenatide were built with a selection procedure, optimizing measurement fits and model complexity, and were included in a pre-existing T2D simulation platform containing glargine models. With the resulting tool, a simulated trial was conducted with 100 in-silico participants with T2D. Individuals were given iGLarLixi either before breakfast or before an evening meal for 2 weeks and daily glycemic profiles were analyzed. In the model, breakfast was considered the largest meal of the day. Results: A similar percentage of time within 24 hours was spent with blood sugar levels between 70 to 180 mg/dL when iGlarLixi was administered pre-breakfast or pre-evening meal (73% vs 71%, respectively). Overall percent of time with blood glucose levels above 180 mg/dL within a 24-hour period was similar when iGlarLixi was administered pre-breakfast or pre-evening meal (26% vs 28%, respectively). Rates of hypoglycemia were low in both regimens, with a blood glucose concentration of below 70 mg/dL only observed for 1% of the 24-hour time period for either timing of administration. Conclusions: Good efficacy was observed when iGlarlixi was administered pre-breakfast; however, administration of iGlarlixi pre-evening meal was also deemed to be effective, even though in the model the size of the evening meal was smaller than that of the breakfast.

scholarly journals The Research of Improved Grey GM (1, 1) Model to Predict the Postprandial Glucose in Type 2 Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Yannian Wang ◽  
Fenfen Wei ◽  
Changqing Sun ◽  
Quanzhong Li
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Prediction Model ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Original Data ◽  
Postprandial Glucose ◽  
Postprandial Blood Glucose ◽  
Glucose Prediction

Diabetes may result in some complications and increase the risk of many serious health problems. The purpose of clinical treatment is to carefully manage the blood glucose concentration. If the blood glucose concentration is predicted, treatments can be taken in advance to reduce the harm to patients. For this purpose, an improved grey GM (1, 1) model is applied to predict blood glucose with a small amount of data, and especially in terms of improved smoothness it can get higher prediction accuracy. The original data of blood glucose of type 2 diabetes is acquired by CGMS. Then the prediction model is established. Finally, 50 cases of blood glucose from the Henan Province People’s Hospital are predicted in 5, 10, 15, 20, 25, and 30 minutes, respectively, in advance to verify the prediction model. The prediction result of blood glucose is evaluated by the EGA, MSE, and MAE. Particularly, the prediction results of postprandial blood glucose are presented and analyzed. The result shows that the improved grey GM (1, 1) model has excellent performance in postprandial blood glucose prediction.

Sitagliptin: A DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

2011 ◽  
Vol 3 ◽  
pp. CMT.S6227 ◽  
Author(s):  
Kathryn MS Johnson ◽  
Kathleen Schurr
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetes Therapy ◽  
High Blood Glucose ◽  
Adverse Side Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) has become an epidemic, with worldwide projections indicating that more than 336 million people will be afflicted with the disease by 2030. T2DM is characterized by inappropriately high blood glucose levels due to a deficiency in insulin secretion, action, or both. Despite the horrific complications that occur with chronic elevations of blood glucose levels, less than half of those with T2DM do not maintain proper glycemic control. Sitagliptin (Januvia, Merck and Co., Whitehouse Station, New Jersey) is a novel diabetes therapy approved for use in the U.S. and Europe. This small molecule inhibits the activity of DPP-4, a peptidase that degrades the glucoregulatory hormone GLP-1. Sitagliptin increases glucoregulation in individuals with T2DM both as a monotherapy and in combination with other antihyperglycemic drugs, with a low risk of adverse side effects.

scholarly journals The liver-alpha-cell axis after a mixed meal and during weight loss in type 2 diabetes

2021 ◽  
Author(s):  
Julia Otten ◽  
Andreas Stomby ◽  
Maria Waling ◽  
Elin Chorell ◽  
Mats Ryberg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Glucagon Secretion ◽  
Alpha Cell ◽  
Cell Axis ◽  
Hepatic Insulin Sensitivity ◽  
Protein Rich

Objective: Glucagon and amino acids may be regulated in a feedback loop called the liver-alpha-cell axis with alanine or glutamine as suggested signal molecules. We assessed this concept in individuals with type 2 diabetes in the fasting state, after ingestion of a protein rich meal and during weight loss. Moreover, we investigated if postprandial glucagon secretion and hepatic insulin sensitivity were related. Methods: This is a secondary analysis of a 12-week weight loss trial (Paleolithic diet ± exercise) in 29 individuals with type 2 diabetes. Before and after the intervention, plasma glucagon and amino acids were measured in the fasting state and during 180 min after a protein-rich mixed meal. Hepatic insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp with [6,6-2H2]glucose as tracer. Results: The postprandial increase of plasma glucagon was associated with the postprandial increase of alanine and several other amino acids but not glutamine. In the fasted state and after the meal, glucagon levels were negatively correlated with hepatic insulin sensitivity (rS = -0.51 / r = -0.58 respectively; both P<0.05). Improved hepatic insulin sensitivity with weight loss was correlated with decreased postprandial glucagon response (r = -0.78; P<0.001). Conclusions: Several amino acids, notably alanine, but not glutamine could be key signals to the alpha cell to increase glucagon secretion. Amino acids may be part of a feedback mechanism as glucagon increases endogenous glucose production and ureagenesis in the liver. Moreover, postprandial glucagon secretion seems to be tightly related to hepatic insulin sensitivity.

The effect of premixed insulin to blood glucose concentration in patients with type 2 diabetes mellitus

2020 ◽  
Vol 30 (6) ◽  
Author(s):  
Arina D. Puspitasari ◽  
Hayu Kusuma ◽  
Dinda M.N. Ratri ◽  
Cahyo Wibisono ◽  
Budi Suprapti
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Postprandial Blood Glucose ◽  
Premixed Insulin ◽  
Acting Insulin ◽  
Blood Glucose Concentrations

AbstractBackgroundOne of the therapies used to treat type 2 diabetes mellitus (T2DM) disease is combination insulin which consists of rapid-acting insulin and intermediate-acting insulin (premixed). This study aimed to examine the profile of premixed insulin related to blood glucose concentration and to identify the drug interactions due to the combination of premixed insulin with other drugs taken by T2DM patients.MethodsThis study was a prospective observational study with cross-sectional data that were analyzed descriptively. The respondents invited were T2DM patients with or without complication or comorbid disease who received premixed insulin with or without a combination of oral antidiabetic therapy in the Outpatient Unit of Universitas Airlangga Hospital, Surabaya. The research instruments used are data sheet, patient medical record, and fasting and postprandial blood glucose concentration.ResultsA total of 118 patients received premixed insulin therapy, but only 80 patients were included in the inclusion criteria. Based on types of insulin, the combination of 30% aspart and 70% protamine aspart was used by 91.25% T2DM patients, and a combination of 25% insulin lispro and 75% protamine lispro was used by 8.75% T2DM patients. There were 30.3% of patients who could achieve the target of 80–130 mg/dL in fasting blood glucose concentrations, and 35.1% of patients achieved the target of ≤180 mg/dL in postprandial blood glucose concentration. Drug interactions may occur in patients who use premixed insulin with glimepiride, lisinopril, fenofibrate, candesartan, irbesartan, and gemfibrozil.ConclusionsIn this study, premixed insulin have not reached the target of fasting and postprandial blood glucose concentrations in most patients.

scholarly journals Cell Autonomous Dysfunction and Insulin Resistance in Pancreatic α Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3699 ◽  
Author(s):  
Norikiyo Honzawa ◽  
Kei Fujimoto ◽  
Tadahiro Kitamura
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Current Knowledge ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Hepatic Glucose

To date, type 2 diabetes is considered to be a “bi-hormonal disorder” rather than an “insulin-centric disorder,” suggesting that glucagon is as important as insulin. Although glucagon increases hepatic glucose production and blood glucose levels, paradoxical glucagon hypersecretion is observed in diabetes. Recently, insulin resistance in pancreatic α cells has been proposed to be associated with glucagon dysregulation. Moreover, cell autonomous dysfunction of α cells is involved in the etiology of diabetes. In this review, we summarize the current knowledge about the physiological and pathological roles of glucagon.

scholarly journals The relationships between glucose variability and renal function in type 2 diabetes patients on basal-bolus insulin therapy

2015 ◽  
Vol 18 (4) ◽  
pp. 66-71 ◽  
Author(s):  
Vadim V. Klimontov ◽  
Natalia E. Myakina
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Blood Glucose ◽  
Insulin Therapy ◽  
Glucose Variability ◽  
High Blood Glucose ◽  
Interstitial Glucose ◽  
Bolus Insulin ◽  
Basal Bolus

Aim. To assess the relationship of glucose variability (GV) and renal function in patients with type 2 diabetes on basal-bolus insulin therapy.Materials and methods. We observed 101 females with type 2 diabetes, aged 47–79 years, with a glomerular filtration rate (GFR) 30 mL/min/1.73 m2. Insulin was combined with metformin in 45 of these women. The mean glucose and standard deviation, continuous overlapping net glucose action, lability index, J-index, low blood glucose index (LBGI), high blood glucose index (HBGI), M-value and mean absolute glucose (MAG) were calculated based on the results of blinded continuous glucose monitoring. The prevalence of episodes of low interstitial glucose (3.9 and 2.8 mmol/L) of at least 20-min duration was estimated.Results. Patients with a GFR of 30–44 mL/min/1.73 m2 had significantly lower HBGI, J-index, MAG and M-value compared with those with better filtration (all p 0.05); LBGI was not dependent on GFR. The GFR values were weakly and positively correlated with HBGI, J-index, M-value and MAG. Multiple regression analysis showed that GFR is an independent predictor of MAG (p = 0.04). No significant differences were found in the prevalence of episodes of low interstitial glucose between patients with different GFR ranges.Conclusions. GV parameters are related to renal function in type 2 diabetic women on basal-bolus insulin therapy. Patients with stage 3b chronic kidney disease have reduced GV, predominantly in the hyperglycaemic band, compared with those with better filtration.

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