Related Experiment Video
Updated: May 14, 2026
12:33
A Method for Mouse Pancreatic Islet Isolation and Intracellular cAMP Determination
Published on: June 25, 2014
Insulin therapy for pre-hyperglycemic beta-cell endoplasmic reticulum crowding.
Afaf Absood1, Benjamin Gandomani, Anthony Zaki
1Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Plos One
|February 15, 2013
Summary
Insulin therapy can improve early diabetes by reducing endoplasmic reticulum (ER) crowding in beta cells. This approach may enhance insulin secretion and glucose tolerance, potentially preventing further metabolic decline.
Area of Science:
- Endocrinology
- Cell Biology
- Metabolic Diseases
Background:
- Type 2 diabetes involves beta-cell dysfunction and loss, particularly in advanced stages.
- Endoplasmic reticulum (ER) stress and crowding impair proinsulin processing and insulin secretion in early diabetes.
- Current therapies are often insufficient for advanced type 2 diabetes.
Purpose of the Study:
- To test the hypothesis that insulin therapy improves beta-cell function by alleviating ER crowding.
- To investigate the effects of insulin therapy on pre-diabetic beta-cell dysfunction in a transgenic mouse model.
Main Methods:
- Utilized hProC(A7)Y-CpepGFP transgenic mice exhibiting ER crowding and proinsulin dysmaturation.
- Administered treat-to-target insulin therapy, carefully managing dosage to avoid hypoglycemia and weight gain.
- Assessed proinsulin maturation, insulin secretion, and glucose tolerance following therapy.
Main Results:
- Insulin therapy successfully attenuated beta-cell ER proinsulin synthesis.
- Alleviation of ER crowding led to transient improvements in proinsulin maturation and insulin secretion.
- Glucose tolerance showed temporary enhancement in treated mice.
Conclusions:
- Treat-to-target insulin therapy can alleviate pre-diabetic ER crowding in beta cells.
- This alleviation may improve beta-cell function and insulin secretion.
- Targeting ER crowding offers a potential strategy to prevent further metabolic deterioration in early diabetes.
Related Concept Videos
01:25Insulin: Biosynthesis, Chemistry, and Preparation
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
01:27Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are co-secreted in...
Insulin and C-peptide are co-secreted in...
01:16Insulin: Dosing Regimen and Adverse Effects
Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
01:05Insulin Secretory Vesicles
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
01:15Diabetes: Management and Pharmacotherapy
The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
01:24Glucagon-like Receptor Agonists
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...