A novel cellular defect in diabetes

Membrane repair failure

Amber C. Howard, Anna K. McNeil, Fei Xiong, Wencheng Xiong, Paul L McNeil

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

OBJECTIVE - Skeletal muscle myopathy is a common diabetes complication. One possible cause of myopathy is myocyte failure to repair contraction-generated plasma membrane injuries. Here, we test the hypothesis that diabetes induces a repair defect in skeletal muscle myocytes. RESEARCH DESIGN AND METHODS - Myocytes in intact muscle from type 1 (INS2 Akita+/-) and type 2 (db/db) diabetic mice were injured with a laser and dye uptake imaged confocally to test repair efficiency. Membrane repair defects were also assessed in diabetic mice after downhill running, which induces myocyte plasma membrane disruption injuries in vivo. A cell culture model was used to investigate the role of advanced glycation end products (AGEs) and the receptor for AGE (RAGE) in development of this repair defect. RESULTS - Diabetic myocytes displayed significantly more dye influx after laser injury than controls, indicating a repair deficiency. Downhill running also resulted in a higher level of repair failure in diabetic mice. This repair defect was mimicked in cultured cells by prolonged exposure to high glucose. Inhibition of the formation of AGE eliminated this glucose-induced repair defect. However, a repair defect could be induced, in the absence of high glucose, by enhancing AGE binding to RAGE, or simply by increasing cell exposure to AGE. CONCLUSIONS - Because one consequence of repair failure is rapid cell death (via necrosis), our demonstration that repair fails in diabetes suggests a new mechanism by which myopathy develops in diabetes.

Original languageEnglish (US)
Pages (from-to)3034-3043
Number of pages10
JournalDiabetes
Volume60
Issue number11
DOIs
StatePublished - Nov 1 2011

Fingerprint

Muscle Cells
Muscular Diseases
Membranes
Glucose
Running
Wounds and Injuries
Skeletal Muscle
Cell Membrane
Dye Lasers
Advanced Glycosylation End Products
Skeletal Muscle Fibers
Diabetes Complications
Cultured Cells
Lasers
Cell Death
Research Design
Necrosis
Coloring Agents
Cell Culture Techniques
Muscles

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Howard, A. C., McNeil, A. K., Xiong, F., Xiong, W., & McNeil, P. L. (2011). A novel cellular defect in diabetes: Membrane repair failure. Diabetes, 60(11), 3034-3043. https://doi.org/10.2337/db11-0851

A novel cellular defect in diabetes : Membrane repair failure. / Howard, Amber C.; McNeil, Anna K.; Xiong, Fei; Xiong, Wencheng; McNeil, Paul L.

In: Diabetes, Vol. 60, No. 11, 01.11.2011, p. 3034-3043.

Research output: Contribution to journalArticle

Howard, AC, McNeil, AK, Xiong, F, Xiong, W & McNeil, PL 2011, 'A novel cellular defect in diabetes: Membrane repair failure', Diabetes, vol. 60, no. 11, pp. 3034-3043. https://doi.org/10.2337/db11-0851
Howard AC, McNeil AK, Xiong F, Xiong W, McNeil PL. A novel cellular defect in diabetes: Membrane repair failure. Diabetes. 2011 Nov 1;60(11):3034-3043. https://doi.org/10.2337/db11-0851
Howard, Amber C. ; McNeil, Anna K. ; Xiong, Fei ; Xiong, Wencheng ; McNeil, Paul L. / A novel cellular defect in diabetes : Membrane repair failure. In: Diabetes. 2011 ; Vol. 60, No. 11. pp. 3034-3043.
@article{f1b1f279ea67472a996ca8fd211648f3,
title = "A novel cellular defect in diabetes: Membrane repair failure",
abstract = "OBJECTIVE - Skeletal muscle myopathy is a common diabetes complication. One possible cause of myopathy is myocyte failure to repair contraction-generated plasma membrane injuries. Here, we test the hypothesis that diabetes induces a repair defect in skeletal muscle myocytes. RESEARCH DESIGN AND METHODS - Myocytes in intact muscle from type 1 (INS2 Akita+/-) and type 2 (db/db) diabetic mice were injured with a laser and dye uptake imaged confocally to test repair efficiency. Membrane repair defects were also assessed in diabetic mice after downhill running, which induces myocyte plasma membrane disruption injuries in vivo. A cell culture model was used to investigate the role of advanced glycation end products (AGEs) and the receptor for AGE (RAGE) in development of this repair defect. RESULTS - Diabetic myocytes displayed significantly more dye influx after laser injury than controls, indicating a repair deficiency. Downhill running also resulted in a higher level of repair failure in diabetic mice. This repair defect was mimicked in cultured cells by prolonged exposure to high glucose. Inhibition of the formation of AGE eliminated this glucose-induced repair defect. However, a repair defect could be induced, in the absence of high glucose, by enhancing AGE binding to RAGE, or simply by increasing cell exposure to AGE. CONCLUSIONS - Because one consequence of repair failure is rapid cell death (via necrosis), our demonstration that repair fails in diabetes suggests a new mechanism by which myopathy develops in diabetes.",
author = "Howard, {Amber C.} and McNeil, {Anna K.} and Fei Xiong and Wencheng Xiong and McNeil, {Paul L}",
year = "2011",
month = "11",
day = "1",
doi = "10.2337/db11-0851",
language = "English (US)",
volume = "60",
pages = "3034--3043",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "11",

}

TY - JOUR

T1 - A novel cellular defect in diabetes

T2 - Membrane repair failure

AU - Howard, Amber C.

AU - McNeil, Anna K.

AU - Xiong, Fei

AU - Xiong, Wencheng

AU - McNeil, Paul L

PY - 2011/11/1

Y1 - 2011/11/1

N2 - OBJECTIVE - Skeletal muscle myopathy is a common diabetes complication. One possible cause of myopathy is myocyte failure to repair contraction-generated plasma membrane injuries. Here, we test the hypothesis that diabetes induces a repair defect in skeletal muscle myocytes. RESEARCH DESIGN AND METHODS - Myocytes in intact muscle from type 1 (INS2 Akita+/-) and type 2 (db/db) diabetic mice were injured with a laser and dye uptake imaged confocally to test repair efficiency. Membrane repair defects were also assessed in diabetic mice after downhill running, which induces myocyte plasma membrane disruption injuries in vivo. A cell culture model was used to investigate the role of advanced glycation end products (AGEs) and the receptor for AGE (RAGE) in development of this repair defect. RESULTS - Diabetic myocytes displayed significantly more dye influx after laser injury than controls, indicating a repair deficiency. Downhill running also resulted in a higher level of repair failure in diabetic mice. This repair defect was mimicked in cultured cells by prolonged exposure to high glucose. Inhibition of the formation of AGE eliminated this glucose-induced repair defect. However, a repair defect could be induced, in the absence of high glucose, by enhancing AGE binding to RAGE, or simply by increasing cell exposure to AGE. CONCLUSIONS - Because one consequence of repair failure is rapid cell death (via necrosis), our demonstration that repair fails in diabetes suggests a new mechanism by which myopathy develops in diabetes.

AB - OBJECTIVE - Skeletal muscle myopathy is a common diabetes complication. One possible cause of myopathy is myocyte failure to repair contraction-generated plasma membrane injuries. Here, we test the hypothesis that diabetes induces a repair defect in skeletal muscle myocytes. RESEARCH DESIGN AND METHODS - Myocytes in intact muscle from type 1 (INS2 Akita+/-) and type 2 (db/db) diabetic mice were injured with a laser and dye uptake imaged confocally to test repair efficiency. Membrane repair defects were also assessed in diabetic mice after downhill running, which induces myocyte plasma membrane disruption injuries in vivo. A cell culture model was used to investigate the role of advanced glycation end products (AGEs) and the receptor for AGE (RAGE) in development of this repair defect. RESULTS - Diabetic myocytes displayed significantly more dye influx after laser injury than controls, indicating a repair deficiency. Downhill running also resulted in a higher level of repair failure in diabetic mice. This repair defect was mimicked in cultured cells by prolonged exposure to high glucose. Inhibition of the formation of AGE eliminated this glucose-induced repair defect. However, a repair defect could be induced, in the absence of high glucose, by enhancing AGE binding to RAGE, or simply by increasing cell exposure to AGE. CONCLUSIONS - Because one consequence of repair failure is rapid cell death (via necrosis), our demonstration that repair fails in diabetes suggests a new mechanism by which myopathy develops in diabetes.

UR - http://www.scopus.com/inward/record.url?scp=80755148627&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80755148627&partnerID=8YFLogxK

U2 - 10.2337/db11-0851

DO - 10.2337/db11-0851

M3 - Article

VL - 60

SP - 3034

EP - 3043

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -