Related Experiment Video
Updated: Oct 10, 2025
08:04
Author Spotlight: Investigating Islet Abnormalities and Function with a Pseudoislet Protocol
Published on: November 3, 2023
2.1K
A hormone complex of FABP4 and nucleoside kinases regulates islet function
Kacey J Prentice1, Jani Saksi1, Lauren T Robertson1
1Sabri Ülker Center for Metabolic Research, Harvard T. H. Chan School of Public Health, Department of Molecular Metabolism, Boston, MA, USA.
Nature
|December 9, 2021
Summary
Fatty-acid-binding protein 4 (FABP4) forms a novel hormone complex, Fabkin, regulating energy balance and beta-cell function. Targeting this complex shows promise for preventing type 1 and type 2 diabetes.
Area of Science:
- Endocrinology and Metabolism
- Molecular Biology
- Cardiovascular Research
Background:
- Adipocyte energy store liberation is vital but dysregulated lipolysis, linked to insulin resistance, disrupts metabolic homeostasis.
- Circulating fatty-acid-binding protein 4 (FABP4) levels correlate with cardiometabolic diseases, but its mechanism of action remains unknown.
Purpose of the Study:
- To elucidate the mechanism of action for hormonal FABP4.
- To investigate the role of FABP4 in regulating extracellular ATP/ADP levels and its impact on beta cells.
- To explore the potential of targeting the FABP4 complex for metabolic disease prevention.
Main Methods:
- Investigated the formation of a functional hormone complex involving FABP4, adenosine kinase (ADK), and nucleoside diphosphate kinase (NDPK).
- Assessed the regulation of extracellular ATP and ADP levels by this complex.
- Evaluated the effects of antibody-mediated targeting of the FABP4 complex on metabolic outcomes and beta-cell function in models of diabetes.
Main Results:
- Demonstrated that hormonal FABP4 forms a complex with ADK and NDPK, termed Fabkin, which regulates extracellular ATP and ADP.
- Identified a significant impact of the Fabkin complex on beta cells, suggesting a role in an adipose-beta-cell endocrine axis.
- Showed that antibody-mediated targeting of the Fabkin complex improves metabolic health, enhances beta-cell function, and preserves beta-cell integrity.
Conclusions:
- The FABP4-ADK-NDPK complex (Fabkin) is a novel hormone regulating energy homeostasis and metabolic organ function.
- Fabkin acts as a key regulator of the adipose-beta-cell axis, influencing lipolysis and beta-cell function.
- Targeting the Fabkin complex offers a promising therapeutic strategy for preventing type 1 and type 2 diabetes and other metabolic diseases.
Related Concept Videos
01:05Insulin Secretory Vesicles
5.9K
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...
5.9K
01:27Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.5K
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...
1.5K
01:28Insulin: The Receptor and Signaling Pathways
1.7K
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...
1.7K
01:16Hormones Regulating Blood Glucose
4.7K
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...
4.7K
01:25Insulin: Biosynthesis, Chemistry, and Preparation
653
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...
653
01:58Cell Specific Gene Expression
14.2K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
14.2K