Related Experiment Video
Updated: May 11, 2025

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
Spatial regulation of glucose and lipid metabolism by hepatic insulin signaling
Baiyu He1, Kyle D Copps1, Oliver Stöhr1
1Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Abstract:
Hepatic insulin sensitivity is critical for systemic glucose and lipid homeostasis. The liver is spatially organized into zones in which hepatocytes express distinct metabolic enzymes; however, the functional significance of this zonation to metabolic dysregulation caused by insulin resistance is undetermined. Here, we used CreER mice to selectively disrupt insulin signaling in periportal (PP) and pericentral (PC) hepatocytes. PP-insulin resistance has been suggested to drive combined hyperglycemia and excess lipogenesis in individuals with type 2 diabetes. However, PP-insulin resistance in mice impaired lipogenesis and suppressed high-fat diet (HFD)-induced hepatosteatosis, despite elevated gluconeogenesis and insulin. In contrast, PC-insulin resistance reduced HFD-induced PC steatosis while preserving normal glucose homeostasis, in part by shifting glycolytic metabolism from the liver to the muscle. These results demonstrate distinct roles of insulin in PP versus PC hepatocytes and suggest that PC-insulin resistance might be therapeutically useful to combat hepatosteatosis without compromising glucose homeostasis.
More Related Videos
08:47Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy
Published on: December 7, 2017
08:13Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
Related Concept Videos
Insulin: The Receptor and Signaling Pathways
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Glucose Homeostasis: Regulation of Blood Glucose
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are...
Cell Specific Gene Expression
Regulation of Food Intake