Life without Proteinase Activated Receptor 2 (PAR2) Alters Body Composition and Glucose Tolerance in Mice.

The potential role of proteinase activated receptor 2 (PAR2) in the development of age-related obesity and insulin resistance is not well-understood. To address the hypothesis that deletion of PAR2 might ameliorate age-related obesity and impaired glucose homeostasis, we assessed body composition and insulin action in 18-month-old male PAR2 knockout (PAR2KO-AG), age-matched (AG) and young C57BL6 (YG, 6-month-old) mice. Body composition was measured by magnetic resonance spectroscopy (MRS) and insulin action was assessed by glucose tolerance (GT), insulin tolerance (IT) and AICAR tolerance (AT) testing.

High-fat diet induced obesity and age influence the telomere shelterin complex and telomerase gene expression in mouse adipose tissue.

Obesity and aging are linked to inflammation and increased risk of chronic disease. Telomeres are the endcaps of chromosomes that are regulated by telomerase, the enzyme that elongates telomeres, as well as a protein complex known as shelterin. Telomere dysfunction is associated with inflammation, aging, and disease.

The impact of age and sex on body composition and glucose sensitivity in C57BL/6J mice.

A paucity of data exists regarding sex differences in age-related obesity and insulin resistance, particularly in the preclinical murine model. The purpose of this study was to determine the effects of age and sex on insulin action and body composition in C57BL/6J mice. Aged (AG, 18 months old) male C57BL/6J mice, glucose tolerance was diminished compared to young (YG, 6 months old) male mice (Area Under Curve: 95,103 ± 6818 vs.

Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice.

Obesity is a major public health problem that is highly associated with insulin resistance and type 2 diabetes, two conditions associated with circadian disruption. To date, dieting is one of the only interventions that result in substantial weight loss, but restricting caloric intake is difficult to maintain long-term. The use of artificial sweeteners, particularly in individuals that consume sugar sweetened beverages (energy drinks, soda), can reduce caloric intake and possibly facilitate weight loss.

Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity.

The superoxide dismutase mimetic manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin (MnTBAP) is a potent antioxidant compound that has been shown to limit weight gain during short-term high fat feeding without preventing insulin resistance. However, whether MnTBAP has therapeutic potential to treat pre-existing obesity and insulin resistance remains unknown. To investigate this, mice were treated with MnTBAP or vehicle during the last five weeks of a 24-week high fat diet (HFD) regimen.

Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice.

Cidea and Cidec play an important role in regulating triglyceride storage in liver and adipose tissue. It is not known if the Cidea and Cidec genes respond to a high fat diet (HFD) or exercise training, two interventions that alter lipid storage. The purpose of the present study was to determine the effect of a HFD and voluntary wheel running (WR) on Cidea and Cidec mRNA and protein expression in adipose tissue and liver of mice.

Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice.

The purpose of the present study was to determine the effect of Akt gene ablation on Akt/Forkhead Box O (FOXO) signaling and atrogene expression. This was accomplished by studying wild-type (WT) and isoform-specific Akt knockout (Akt1(-/-) and Akt2(-/-)) mice. The ability of insulin to promote Akt phosphorylation on Ser(473) was significantly lower in extensor digitorum longus (EDL) and soleus muscles from Akt1(-/-) and Akt2(-/-) mice compared with WT mice.

PKB signaling and atrogene expression in skeletal muscle of aged mice.

The purpose of this study was to determine if PKB signaling is decreased and contractile protein degradation is increased in extensor digitorum longus (EDL) and soleus (SOL) muscles from middle-aged (MA) and aged (AG) mice. We also examined the effect of age on atrogene expression in quadriceps muscle. PKB activity, as assessed by Thr(308) and Ser(473) phosphorylation, was significantly higher in EDL and SOL muscles from AG than MA mice.

Insulin resistance without elevated mammalian target of rapamycin complex 1 activity in muscles of mice fed a high-fat diet.

The mammalian target of rapamycin complex 1 (mTORC1) appears to mediate the development of insulin resistance in cultured cells. We studied in vivo insulin action and mTORC1 signaling in skeletal muscles of mice fed a normal chow [control (CON)] diet or a high-fat diet (HFD) for 16 wk. We assessed in vivo insulin action by measuring glucose tolerance (GT), insulin tolerance (IT), and insulin-assisted GT (IAGT).

Rapamycin does not improve insulin sensitivity despite elevated mammalian target of rapamycin complex 1 activity in muscles of ob/ob mice.

Studies of cultured cells have indicated that the mammalian target of rapamycin complex 1 (mTORC1) mediates the development of insulin resistance. Because a role for mTORC1 in the development of skeletal muscle insulin resistance has not been established, we studied mTORC1 activity in skeletal muscles of ob/ob (OB) mice and wild-type (WT) mice. In vivo insulin action was assessed in muscles of mice 15 min following an intraperitoneal injection of insulin or an equivalent volume of saline.

Regional differences in glucose clearance: effects of insulin and resistance training on arm and leg glucose clearance in older hypertensive individuals.

The purpose of this study was to compare insulin's ability to stimulate glucose uptake in the arm and leg in a group of older hypertensive individuals (n = 13, 66 +/- 2 yr old). We also examined the effect of a 4-mo whole body resistance-training (RT) program on arm and leg glucose clearance (GC) during a hyperinsulinemic-euglycemic clamp. During the hyperinsulinemic-euglycemic clamp, GC was assessed by simultaneous measurement of arm and leg blood flow (BF) and assessment of fractional glucose extraction (GE) in blood samples from the brachial artery, brachial vein, and popliteal vein.

Effect of aerobic exercise training on renal responses to sodium in hypertensives.

Introduction: Aerobic exercise training has been shown to improve cardiovascular function and lower blood pressure (BP) in older adults. The exact mechanism(s) by which aerobic exercise training elicits these changes are unknown; however, it is possible that changes in renal hemodynamics may play a role.

Purpose: The present study was undertaken to examine the effect of aerobic exercise training on renal hemodynamics in older hypertensive individuals.

Effects of insulin and transgenic overexpression of UDP-glucose pyrophosphorylase on UDP-glucose and glycogen accumulation in skeletal muscle fibers.

UDP-glucose (UDP-Glc) and glycogen levels in skeletal muscle fibers of defined fiber type were measured using microanalytical methods. Infusing rats with insulin increased glycogen in both Type I and Type II fibers. Insulin was without effect on UDP-Glc in Type I fibers but decreased UDP-Glc by 35-40% in Type IIA/D and Type IIB fibers.

Effects of aerobic exercise training on the protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway in aged skeletal muscle.

The protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway is thought to play a critical role in the regulation of protein synthesis and skeletal muscle mass. The purpose of the present study was to determine the effects of voluntary wheel running on the PKB/mTOR signaling pathway in muscles from aged mice (20-22 months). The total levels of mTOR were 65% higher in gastrocnemius muscles from aged mice subjected to wheel running compared to aged sedentary mice (p-0.

Resistance training enhances insulin-mediated glucose disposal with minimal effect on the tumor necrosis factor-alpha system in older hypertensives.

The purpose of the present study was to determine if the improvement in insulin sensitivity after resistance training (RT) is associated with a decline in plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-alpha receptor 1 (sTNF R1), and soluble TNF receptor 2 (sTNF R2). Eleven older hypertensives (5 men/6 women, 67 +/- 2 years) participated in a 4-month RT program. Following RT there was a significant increase in upper body (P =.

Aerobic exercise training improves insulin sensitivity independent of plasma tumor necrosis factor-alpha levels in older female hypertensives.

The purpose of the present study was to determine if the improvement in insulin sensitivity following aerobic exercise training (AEX) is associated with a decline in plasma tumor necrosis factor-alpha (TNF-alpha) levels. Fourteen older hypertensive females (age, 62 +/- 2 years) participated in a 6-month AEX program. Following AEX there was a significant increase in maximal aerobic capacity (VO(2)max) (P =.

Exercise-induced changes in insulin action are associated with ACE gene polymorphisms in older adults.

We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 +/- 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (S(I)), assessed by the frequently sampled intravenous glucose tolerance test, was significantly (P = 0.0001) increased following AEX.

Effect of age on skeletal muscle proteolysis in extensor digitorum longus muscles of B6C3F1 mice.

The purpose of this study was to determine if age-related muscle atrophy is associated with an increased rate of protein degradation in extensor digitorum longus (EDL) muscles from young (YG; 2-4 months), middle-aged (MA; 12-17 months), and aged (AG; 22-24 months) B6C3F1 mice. EDL muscles from AG mice weighed less than EDL muscles from MA mice (p =.01).

Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load.

We have investigated the effects of insulin, amino acids, and the degree of muscle loading on the phosphorylation of Ser(2448), a site in the mammalian target of rapamycin (mTOR) phosphorylated by protein kinase B (PKB) in vitro. Phosphorylation was assessed by immunoblotting with a phosphospecific antibody (anti-Ser(P)(2448)) and with mTAb1, an activating antibody whose binding is inhibited by phosphorylation in the region of mTOR that contains Ser(2448). Incubating rat diaphragm muscles with insulin increased Ser(2448) phosphorylation but did not change the total amount of mTOR.