Related Experiment Video
Updated: Jan 22, 2026
05:52
Insulin Injection and Hemolymph Extraction to Measure Insulin Sensitivity in Adult Drosophila melanogaster
Published on: June 30, 2011
20.3K
Insulin: still a miracle after all these years
Fabrizio Barbetti1, Simeon I Taylor2
1Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
The Journal of Clinical Investigation
|July 3, 2019
Summary
Long-term insulin dependence in type 1 diabetes doesn't always mean complete beta cell loss. Some patients retain insulin-producing cells and metabolic responsiveness, with genetic analysis revealing potential alternative diagnoses.
Area of Science:
- Endocrinology
- Genetics
- Immunology
Background:
- Insulin discovery dramatically improved type 1 diabetes (T1D) outcomes.
- The Joslin Medalist Study examines T1D patients with ≥50 years of insulin dependence.
- Understanding long-term T1D pathophysiology is crucial for optimizing patient care.
Purpose of the Study:
- To investigate the characteristics of long-term insulin-dependent T1D patients (Medalists).
- To evaluate genetic factors, immune status, and residual beta cell function in Medalists.
- To explore potential alternative diagnoses within the Medalist cohort.
Main Methods:
- Analysis of HLA variants and autoantibody status.
- Assessment of beta cell function and C-peptide release.
- Monogenetic diabetes gene evaluation and REVEL classification.
- Postmortem pancreatic tissue analysis.
Main Results:
- Postmortem pancreata showed insulin-positive beta cells in Medalists.
- Some patients maintained metabolic response despite long-term insulin use.
- The Medalist cohort exhibited significant heterogeneity.
- Genetic testing indicated some patients may not have T1D based on REVEL classification.
Conclusions:
- Residual beta cell function and insulin production can persist in long-term T1D.
- The Medalist cohort is genetically diverse, suggesting alternative diabetes classifications.
- Genetic insights may guide personalized therapy adjustments for some long-term T1D patients.
Related Concept Videos
01:05Insulin Secretory Vesicles
6.4K
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...
6.4K
01:28Insulin: The Receptor and Signaling Pathways
2.9K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
2.9K
01:27Insulin Formulations: Types and Delivery
671
Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.
Short-acting insulins are divided into...
Short-acting insulins are divided into...
671
01:25Insulin: Biosynthesis, Chemistry, and Preparation
1.3K
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...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
1.3K
01:16Insulin: Dosing Regimen and Adverse Effects
705
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...
705
01:27Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
2.2K
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...
Insulin and C-peptide are...
2.2K