Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways

A., Khan; J., Pessin

doi:10.1007/s00125-002-0974-7

Cited by 438Metabolism, Diabetes, and CancerCaveolin-1 and cellular processesPancreatic function and diabetes

Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways

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A., Khan, J., Pessin·2002·Diabetologia

DOI 10.1007/s00125-002-0974-7

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Abstract

Insulin-stimulated glucose uptake in adipose tissue and striated muscle is critical for reducing post-prandial blood glucose concentrations and the dysregulation of this process is one hallmark of Type II (non-insulin-dependent) diabetes mellitus. It has been well established that the insulin-stimulated redistribution of the insulin responsive glucose transporter, GLUT-4, from intracellular storage sites to the plasma membrane depends on the production of phosphoinositide 3,4,5 trisphosphate by the Class IA Phosphatidylinositol 3' kinase. Recent discoveries however, have shown the presence of a second insulin signalling pathway leading to GLUT-4 translocation, a pathway dependent on insulin receptor signalling emanating from caveolae or lipid rafts at the plasma membrane. This pathway begins with the phosphorylation of the adaptor protein Cbl by the insulin receptor, and results in the activation of a small GTP binding protein, TC10, a member of the Rho family. TC10 is able to modulate actin structure in 3T3L1 adipocytes, and its overexpression inhibits insulin-stimulated GLUT-4 translocation, an inhibition completely dependent on localization of TC10 to the caveolae or lipid rafts. The spatial compartmentalization of insulin signalling from caveolae or lipid rafts provides a novel signalling pathway that functions in concert with general signalling mechanisms in the control of actin dynamics regulating insulin-dependent GLUT-4 translocation.

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After docking to its receptor on muscle and adipose tissue, insulin enables insulin-dependent uptake of glucose into these tissues and lowers blood glucose levels by removing exogenous glucose from the bloodstream.
“After docking to its receptor on muscle and adipose tissue, insulin enables the insulin-dependent uptake of glucose into these tissues and hence lowers blood glucose levels by removing the exogenous glucose from the blood stream (Figure 2).11, 12, 13”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [11]
Insulin's interplay with adipose and muscle tissues is broadly based on facilitating insulin-dependent glucose uptake through GLUT4.
“On one hand, insulin's interplay with adipose and muscle tissues is broadly based on facilitating insulin-dependent glucose uptake through the glucose transporter 4 (GLUT4).11, 12, 13”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [11]

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WANG, Q., BILAN, P. J., Tsakiridis, T. K., et al. (1999) · Biochemical Journal · doi:10.1042/bj3410861v · Cited by 9 · see citing works

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Authors: A., K., & J., P.
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2002-11-01
Volume: 45
Issue: 11
Pages: 1475-1483
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-002-0974-7
OpenAlex: W2033256254
Cited by: 438
References: 73
Citations by year: 2026: 4 · 2025: 9 · 2024: 11 · 2023: 15 · 2022: 11 · 2021: 14 · 2020: 15 · 2019: 19 · 2018: 15 · 2017: 12 · 2016: 16 · 2015: 17 · 2014: 19 · 2013: 19 · 2012: 26
FWCI: 8.29
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Diabetologia (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords: insulin signaling, glucose uptake, GLUT4 translocation, type 2 diabetes, phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3-kinase, insulin receptor, caveolae, lipid rafts, TC10, Rho GTPases, actin dynamics, adipocytes, skeletal muscle
MeSH terms: Animals, Diabetes Mellitus, Glucose, Humans, Insulin, Monosaccharide Transport Proteins, Muscle Proteins, Signal Transduction, GTP-Binding Proteins, Phosphatidylinositol 3-Kinases, Glucose Transporter Type 4

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Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways

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