Related Experiment Video
Updated: May 20, 2026
08:03
Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
Published on: June 25, 2017
The HMGA1-IGF-I/IGFBP system: a novel pathway for modulating glucose uptake
Stefania Iiritano1, Eusebio Chiefari, Valeria Ventura
1Dipartimento di Scienze della Salute, Università di Catanzaro Magna Græcia, 88100 Catanzaro, Italy.
Molecular Endocrinology (Baltimore, Md.)
|June 30, 2012
Summary
High mobility group A1 (HMGA1) protein loss impairs insulin signaling but activates compensatory insulin-independent glucose uptake pathways. HMGA1 regulates IGF-binding proteins, enhancing glucose disposal and protecting against hyperglycemia.
Area of Science:
- Molecular Biology
- Metabolic Regulation
- Endocrinology
Background:
- Loss of High Mobility Group A1 (HMGA1) protein expression in mice leads to a type 2-like diabetic phenotype with decreased insulin receptor expression.
- Paradoxically, this phenotype is associated with increased peripheral insulin sensitivity, suggesting compensatory glucose disposal mechanisms.
- These adaptations promote glucose uptake via insulin-independent processes, potentially protecting against hyperglycemia.
Purpose of the Study:
- To investigate the compensatory pathways involved in glucose uptake in the absence of HMGA1.
- To elucidate the role of HMGA1 in the regulation of insulin-independent glucose disposal mechanisms.
- To explore the connection between HMGA1, IGF-binding proteins, and glucose metabolism.
Main Methods:
- Chromatin immunoprecipitation and protein-protein interaction studies.
- Transient transcription assays in living cells.
- Positron emission tomography with (18)F-FDG and euglycemic clamp with IGF-I in Hmga1-knockout mice.
Main Results:
- HMGA1 is essential for the gene activation of IGF-binding proteins 1 (IGFBP1) and 3 (IGFBP3).
- IGF-I bioactivity is increased in Hmga1-knockout mice.
- Skeletal muscle Glut4 protein expression and glucose uptake are enhanced in Hmga1-knockout mice compared to wild-type littermates.
Conclusions:
- HMGA1 modulates IGF-I activity by affecting IGFBP expression.
- HMGA1 acts as a novel mediator of glucose disposal.
- Activation of insulin-independent pathways regulated by HMGA1 may protect against hyperglycemia.
Related Concept Videos
01:28Insulin: The Receptor and Signaling Pathways
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 this inhibition is released...
01:16Hormones Regulating Blood Glucose
Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
In addition to accelerating glucose uptake and utilization, insulin has...
01:02Glucose Homeostasis: Regulation of Blood Glucose
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
01:26Glucose Absorption Into the Small Intestine
Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and 'exit' via the...
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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...