Nine days of intensive exercise training improves mitochondrial function but not insulin action in adult offspring of mothers with type 2 diabetes

Brian A. Irving, Kevin R. Short, K Sreekumaran Nair, Craig S. Stump

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Context: A close association between insulin resistance and reduced skeletal muscle oxidative capacity has been reported in adult offspring of people with type 2 diabetes (T2D), prompting a hypothesis that insulin resistance may result from mitochondrial dysfunction or vice versa. Objective: We determined whether 9 d of intensive exercise training ameliorates the mitochondrial dysfunction and insulin resistance in offspring of T2D. Methods: We compared the response to 9 d of intensive exercise training in eight (seven females, one male) healthy adult offspring of mothers with T2D with eight (six females, two males) non-diabetic controls. Skeletal muscle mitochondrial ATP production was assessed using a luciferase-based assay, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamps. Results: Short-term intensive training increased skeletal muscle mitochondrial ATP production and citrate synthase activity similarly in both groups (P < 0.01). In contrast, whereas short-term intensive training reduced the fasting glucose (∼5%, P = 0.035) and insulin levels (∼40%, P = 0.011) as well as increased the glucose infusion rate during the hyperinsulinemic-euglycemic clamp (∼50%, P = 0.028) among controls, no changes in these parameters were observed among offspring except for an increase in fasting glucose (∼7%, P = 0.004). Conclusion: A short-term intensive exercise training program was equally effective at increasing skeletal muscle oxidative capacity in nondiabetic people and in the offspring of mothers with diabetes. In contrast, the exercise improved insulin sensitivity only in nondiabetic people but not in the offspring of T2D mothers, revealing dissociation between improvements in skeletal muscle mitochondrial function and insulin sensitivity. The exercise effect on mitochondrial function and insulin sensitivity seems to be mediated by different regulatory pathways.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number7
DOIs
StatePublished - Jul 1 2011

Fingerprint

Medical problems
Type 2 Diabetes Mellitus
Insulin Resistance
Exercise
Insulin
Skeletal Muscle
Muscle
Glucose Clamp Technique
Glucose
Clamping devices
Fasting
Mitochondrial Proton-Translocating ATPases
ATP Citrate (pro-S)-Lyase
Adenosine Triphosphate
Citrate (si)-Synthase
Luciferases
Assays
Education
Association reactions

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{e84cd9f47f074e36b3d5de22a3d42b78,
title = "Nine days of intensive exercise training improves mitochondrial function but not insulin action in adult offspring of mothers with type 2 diabetes",
abstract = "Context: A close association between insulin resistance and reduced skeletal muscle oxidative capacity has been reported in adult offspring of people with type 2 diabetes (T2D), prompting a hypothesis that insulin resistance may result from mitochondrial dysfunction or vice versa. Objective: We determined whether 9 d of intensive exercise training ameliorates the mitochondrial dysfunction and insulin resistance in offspring of T2D. Methods: We compared the response to 9 d of intensive exercise training in eight (seven females, one male) healthy adult offspring of mothers with T2D with eight (six females, two males) non-diabetic controls. Skeletal muscle mitochondrial ATP production was assessed using a luciferase-based assay, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamps. Results: Short-term intensive training increased skeletal muscle mitochondrial ATP production and citrate synthase activity similarly in both groups (P < 0.01). In contrast, whereas short-term intensive training reduced the fasting glucose (∼5{\%}, P = 0.035) and insulin levels (∼40{\%}, P = 0.011) as well as increased the glucose infusion rate during the hyperinsulinemic-euglycemic clamp (∼50{\%}, P = 0.028) among controls, no changes in these parameters were observed among offspring except for an increase in fasting glucose (∼7{\%}, P = 0.004). Conclusion: A short-term intensive exercise training program was equally effective at increasing skeletal muscle oxidative capacity in nondiabetic people and in the offspring of mothers with diabetes. In contrast, the exercise improved insulin sensitivity only in nondiabetic people but not in the offspring of T2D mothers, revealing dissociation between improvements in skeletal muscle mitochondrial function and insulin sensitivity. The exercise effect on mitochondrial function and insulin sensitivity seems to be mediated by different regulatory pathways.",
author = "Irving, {Brian A.} and Short, {Kevin R.} and Nair, {K Sreekumaran} and Stump, {Craig S.}",
year = "2011",
month = "7",
day = "1",
doi = "10.1210/jc.2010-2863",
language = "English (US)",
volume = "96",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "7",

}

TY - JOUR

T1 - Nine days of intensive exercise training improves mitochondrial function but not insulin action in adult offspring of mothers with type 2 diabetes

AU - Irving, Brian A.

AU - Short, Kevin R.

AU - Nair, K Sreekumaran

AU - Stump, Craig S.

PY - 2011/7/1

Y1 - 2011/7/1

N2 - Context: A close association between insulin resistance and reduced skeletal muscle oxidative capacity has been reported in adult offspring of people with type 2 diabetes (T2D), prompting a hypothesis that insulin resistance may result from mitochondrial dysfunction or vice versa. Objective: We determined whether 9 d of intensive exercise training ameliorates the mitochondrial dysfunction and insulin resistance in offspring of T2D. Methods: We compared the response to 9 d of intensive exercise training in eight (seven females, one male) healthy adult offspring of mothers with T2D with eight (six females, two males) non-diabetic controls. Skeletal muscle mitochondrial ATP production was assessed using a luciferase-based assay, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamps. Results: Short-term intensive training increased skeletal muscle mitochondrial ATP production and citrate synthase activity similarly in both groups (P < 0.01). In contrast, whereas short-term intensive training reduced the fasting glucose (∼5%, P = 0.035) and insulin levels (∼40%, P = 0.011) as well as increased the glucose infusion rate during the hyperinsulinemic-euglycemic clamp (∼50%, P = 0.028) among controls, no changes in these parameters were observed among offspring except for an increase in fasting glucose (∼7%, P = 0.004). Conclusion: A short-term intensive exercise training program was equally effective at increasing skeletal muscle oxidative capacity in nondiabetic people and in the offspring of mothers with diabetes. In contrast, the exercise improved insulin sensitivity only in nondiabetic people but not in the offspring of T2D mothers, revealing dissociation between improvements in skeletal muscle mitochondrial function and insulin sensitivity. The exercise effect on mitochondrial function and insulin sensitivity seems to be mediated by different regulatory pathways.

AB - Context: A close association between insulin resistance and reduced skeletal muscle oxidative capacity has been reported in adult offspring of people with type 2 diabetes (T2D), prompting a hypothesis that insulin resistance may result from mitochondrial dysfunction or vice versa. Objective: We determined whether 9 d of intensive exercise training ameliorates the mitochondrial dysfunction and insulin resistance in offspring of T2D. Methods: We compared the response to 9 d of intensive exercise training in eight (seven females, one male) healthy adult offspring of mothers with T2D with eight (six females, two males) non-diabetic controls. Skeletal muscle mitochondrial ATP production was assessed using a luciferase-based assay, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamps. Results: Short-term intensive training increased skeletal muscle mitochondrial ATP production and citrate synthase activity similarly in both groups (P < 0.01). In contrast, whereas short-term intensive training reduced the fasting glucose (∼5%, P = 0.035) and insulin levels (∼40%, P = 0.011) as well as increased the glucose infusion rate during the hyperinsulinemic-euglycemic clamp (∼50%, P = 0.028) among controls, no changes in these parameters were observed among offspring except for an increase in fasting glucose (∼7%, P = 0.004). Conclusion: A short-term intensive exercise training program was equally effective at increasing skeletal muscle oxidative capacity in nondiabetic people and in the offspring of mothers with diabetes. In contrast, the exercise improved insulin sensitivity only in nondiabetic people but not in the offspring of T2D mothers, revealing dissociation between improvements in skeletal muscle mitochondrial function and insulin sensitivity. The exercise effect on mitochondrial function and insulin sensitivity seems to be mediated by different regulatory pathways.

UR - http://www.scopus.com/inward/record.url?scp=79960093279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960093279&partnerID=8YFLogxK

U2 - 10.1210/jc.2010-2863

DO - 10.1210/jc.2010-2863

M3 - Article

C2 - 21508128

AN - SCOPUS:79960093279

VL - 96

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -