Impaired oxidative phosphorylation in skeletal muscle of intrauterine growth-retarded rats

2003 ◽  
Vol 285 (1) ◽  
pp. E130-E137 ◽  
Author(s):  
Mary A. Selak ◽  
Bayard T. Storey ◽  
Iyalla Peterside ◽  
Rebecca A. Simmons
Keyword(s):  
Type 2 Diabetes ◽  
Oxidative Phosphorylation ◽  
Growth Retardation ◽  
Pyruvate Dehydrogenase ◽  
Intrauterine Growth Retardation ◽  
Glycogen Synthesis ◽  
Later Life ◽  
Pyruvate Dehydrogenase Kinase ◽  
Intrauterine Growth

Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in later life. We have developed a model of uteroplacental insufficiency, a common cause of intrauterine growth retardation, in the rat. Early in life, the animals are insulin resistant and by 6 mo of age they develop diabetes. Glycogen content and insulin-stimulated 2-deoxyglucose uptake were significantly decreased in muscle from IUGR rats. IUGR muscle mitochondria exhibited significantly decreased rates of state 3 oxygen consumption with pyruvate, glutamate, α-ketoglutarate, and succinate. Decreased pyruvate oxidation in IUGR mitochondria was associated with decreased ATP production, decreased pyruvate dehydrogenase activity, and increased expression of pyruvate dehydrogenase kinase 4. Such a defect in IUGR mitochondria leads to a chronic reduction in the supply of ATP available from oxidative phosphorylation. Impaired ATP synthesis in muscle compromises energy-dependent GLUT4 recruitment to the cell surface, glucose transport, and glycogen synthesis, which contribute to insulin resistance and hyperglycemia of type 2 diabetes.

scholarly journals Intrauterine Growth Retardation Leads to the Development of Type 2 Diabetes in the Rat

Diabetes ◽  
2001 ◽  
Vol 50 (10) ◽  
pp. 2279-2286 ◽  
Author(s):  
R. A. Simmons ◽  
L. J. Templeton ◽  
S. J. Gertz
Keyword(s):  
Type 2 Diabetes ◽  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
Intrauterine Growth

scholarly journals Epigenetic Changes Predisposing to Type 2 Diabetes in Intrauterine Growth Retardation

2010 ◽  
Vol 1 ◽  
Author(s):  
Alice Liguori ◽  
Antonella Puglianiello ◽  
Daniela Germani ◽  
Annalisa Deodati ◽  
Emanuela Peschiaroli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Retardation ◽  
Intrauterine Growth Retardation ◽  
Epigenetic Changes ◽  
Intrauterine Growth

scholarly journals The Effect of Periodic Exercise and Resveratrol Supplementation on the Expression of Pparg Coactivator-1 Alpha and Pyruvate Dehydrogenase Kinase Genes in Gastrocnemius Muscle of Old Rats With Type 2 Diabetes

2020 ◽  
Vol 26 (1) ◽  
pp. 68-81
Author(s):  
Ali Salehi ◽  
◽  
Hajar Abbaszadeh ◽  
Parvin Farzanegi ◽  
◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Pyruvate Dehydrogenase ◽  
Gastrocnemius Muscle ◽  
Diabetic Control ◽  
Pyruvate Dehydrogenase Kinase ◽  
Male Rats ◽  
Expression Levels ◽  
Old Rats

Aims: Type 2 diabetes is the result of complex interactions between genetic and environmental factors that affect fat and glucose metabolism. The purpose of this study was to determine the effect of periodic exercise and resveratrol supplement on the expression levels of Pparg Coactivator 1-Alpha (PGC-1α) and Pyruvate Dehydrogenase Kinase (PDK4) genes in gastrocnemius muscle of old rates with type 2 diabetes. Methods & Materials: 42 male rats (mean age= 40-50 weeks; mean body weight= 250-300 g) were randomly divided into 6 groups: healthy-control, diabetic-control, Diabetic+Periodic Exercise, Diabetic+Supplement, Diabetic+Periodic Exercise+Supplement and Saline. The type 2 diabetes was induced by intraperitoneal injection of Streptozotocin (50 mg/kg body weight). The exercise protocol consisted of 10 sets of 1-min activities at 50% intensity and a 2-min rest period between sets, and each week the speed was increased by 2 meters per minute. The exercises were performed for eight weeks. Resveratrol supplement was injected intraperitoneally daily at a dose of 20 mg/kg body weight. The expressions of PDK4 and PGC-1α in the gastrocnemius muscle were measured by real time Polymerase Chain Reaction (PCR) method. Findings: highest expression level of PDK4 and PGC-1α genes in gastrocnemius muscle was observed in the diabetic group received both periodic exercise and Resveratrol supplement and the lowest level was reported in the diabetic-control and saline groups. Conclusion The combination of resveratrol supplementation and periodic exercise can have beneficial effects on PDK4 and PGC-1α expression levels in the gastrocnemius muscle of old rats with type 2 diabetes and reduce the risks of diabetes-related complications.

scholarly journals Metabolomics Reveals Relationship between Plasma Inositols and Birth Weight: Possible Markers for Fetal Programming of Type 2 Diabetes

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Pia Marlene Nissen ◽  
Caroline Nebel ◽  
Niels Oksbjerg ◽  
Hanne Christine Bertram
Keyword(s):  
Type 2 Diabetes ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Intrauterine Growth Restriction ◽  
Later Life ◽  
Epidemiological Studies ◽  
High Birth Weight ◽  
Natural Form ◽  
Intrauterine Growth

Epidemiological studies in man and with experimental animal models have shown that intrauterine growth restriction (IUGR) resulting in low birth weight is associated with higher risk of programming welfare diseases in later life. In the pig, severe IUGR occurs naturally and contribute substantially to a large intralitter variation in birth weight and may therefore be a good model for man. In the present paper the natural form of IUGR in pigs was studied close to term by nuclear magnetic resonance (NMR-)based metabolomics. The NMR-based investigations revealed different metabolic profiles of plasma samples from low-birth weight (LW) and high-birth weight (HW) piglets, respectively, and differences were assigned to levels of glucose and myo-inositol. Further studies by GC-MS revealed that LW piglets had a significant higher concentration of myoinositol and D-chiro-inositol in plasma compared to larger littermates. Myo-inositol and D-chiro-inositol have been coupled with glucose intolerance and insulin resistance in adults, and the present paper therefore suggests that IUGR is related to impaired glucose metabolism during fetal development, which may cause type 2 diabetes in adulthood.

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