Related Experiment Video
Updated: May 8, 2026
08:32
Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
Targeting gp130 to prevent inflammation and promote insulin action
M J Kraakman1, T L Allen, M Whitham
1Cellular & Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
Diabetes, Obesity & Metabolism
|September 6, 2013
Summary
Interleukin-6 (IL-6) plays a role in metabolic diseases like obesity and type 2 diabetes. Blocking IL-6 trans-signalling may offer new therapeutic strategies for these conditions.
Area of Science:
- Metabolic diseases
- Inflammation biology
- Cytokine signaling
Background:
- Obesity and type 2 diabetes are prevalent metabolic diseases.
- Obesity causes chronic low-grade inflammation in key tissues.
- Interleukin-6 (IL-6) and gp130 receptor complex are implicated in inflammation.
Purpose of the Study:
- Investigate the role of IL-6 signaling in metabolic diseases.
- Explore blocking IL-6 trans-signalling to reduce inflammation.
- Examine activating membrane-bound IL-6 signaling to enhance insulin sensitivity.
Main Methods:
- Focus on IL-6 trans-signalling pathways.
- Analyze IL-6-like cytokine activity via the gp130 receptor complex.
Main Results:
- IL-6 is associated with inflammatory diseases like rheumatoid arthritis and cancer.
- Tocilizumab, an IL-6 receptor inhibitor, treats rheumatoid arthritis.
- Blocking IL-6 may have side effects that paradoxically promote metabolic disease.
Conclusions:
- Targeting IL-6 signaling presents potential therapeutic avenues for metabolic diseases.
- Differential modulation of IL-6 signaling pathways is crucial.
- Further research is needed to optimize IL-6-based therapies for metabolic disorders.
Related Concept Videos
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...
01:23Dipeptidyl Peptidase 4 Inhibitors
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
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...
01:25Insulin: 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...
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood glucose levels...
01:26Type I Diabetes II: Pathophysiology
Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular uptake of...