A Thiazolidinedione Improves In Vivo Insulin Action on Skeletal Muscle Glycogen Synthase in Insulin-Resistant Monkeys

Thiazolidinediones (TZD) have been shown to have anti-diabetic effects including the ability to decrease fasting hyperglycemia and hyperinsulinemia, increase insulin-mediated glucose disposal rate (M) and decrease hepatic glucose production, but the mechanisms of action are not well established. To determine whether a TZD (R-102380, Sankyo Company Ltd., Tokyo, Japan) could improve insulin action on skeletal muscle glycogen synthase (GS), the rate-limiting enzyme in glycogen synthesis, 4 insulin-resistant obese monkeys were given I mg/kg/ day R-102380 p.o. for a 6-week period. Skeletal muscle GS activity and glucose 6-phosphate (G6P) content were compared between pre-dosing and dosing periods before and during the maximal insulin-stimulation of a euglycemic hyperinsulinemic clamp

Effects of Proximity between Companion Dogs and Their Caregivers on Heart Rate Variability Measures in Older Adults: A Pilot Study

Heart rate variability (HRV) is a noninvasive tool used to evaluate autonomic nervous system function and is affected by age, stress, postural changes, and physical activity. Dog ownership has been associated with higher 24-hr HRV and increased physical activity compared to nonowners. The current pilot study was designed to evaluate the effects of proximity to a dog in real time (minute-by-minute) on older dog caregivers’ HRV measures and stress index during normal daily life over a 24-hr period. Eleven caregivers (56–83 years of age) wore ActiGraph GT9X Link accelerometers and camntech electrocardiogram monitors, and 11 dogs wore PetPace Collars and ActiGraph monitors to determine (a) proximity (absence or presence of Received Signal Strength Indicator, RSSI), (b) heart rate and HRV measures, (c) position (lying vs. sitting vs. standing), and (d) physical activity in the 11 dyads. Twenty-four hour HRV (SDNN index) and physical activity in the caregivers and dogs were related. Stress index was lower, and HRV parameters (SDNN, rMSDD, high frequency power (HF)) were higher when an RSSI signal was detected (presence of dog) compared to no RSSI signal (absence of dog) in the caregivers while inactive (lying + sitting + standing combined). HRV parameters (rMSDD and HF) were lower in the caregivers while standing and sitting compared to lying. The results from this pilot study support the hypothesis that spending time in the presence of a companion dog increases caregivers’ HRV throughout the day and suggest that proximity to a dog may contribute to overall improvements in 24-hr HRV and cardiac health in dog caregivers

Companion Dog Foster Caregiver Program for Older Veterans at the VA Maryland Health Care System: A Feasibility Study

Veterans experience mental health conditions at a disproportionate rate compared to their civilian counterparts, and approximately 60% of older veterans who receive their care through the United States Department of Veterans Affairs (VA) do not meet physical activity (PA) recommendations. We tested the Veterans as Foster Ambassadors program at the VA Maryland Health Care System to examine whether fostering a companion dog would improve PA and function, heart rate variability (HRV), balance, and quality of life (QOL) in older veterans. Participants wore an accelerometer for ≥10 days during each phase (30 day baseline vs. 60 day foster period) to measure daily PA (n = 4). Six-minute walk (6MW) and balance testing (n = 4) and 24 h heart rate (HR) and HRV (n = 2) were determined at baseline and during the foster period. Compared to baseline, there were significant increases in (a) distance during the 6MW, (b) daily steps, and (c) time spent in moderate activity during the foster period. 24 h HR decreased and time- and frequency-domain measures of HRV significantly increased in a veteran with post-traumatic stress disorder during the foster period compared to baseline. All veterans offered positive feedback about the program and indicated that it was beneficial to them. The results from this pilot study provide evidence that fostering a companion dog can improve PA, health, and QOL in older veterans. Future research conducted with a larger sample size to validate the results is warranted

Combining Actigraph Link and PetPace Collar Data to Measure Activity, Proximity, and Physiological Responses in Freely Moving Dogs in a Natural Environment

Although several studies have examined the effects of an owner’s absence and presence on a dog’s physiological responses under experimental conditions over short periods of time (minutes), little is known about the effects of proximity between humans and freely moving dogs under natural conditions over longer periods of time (days). The first aim of our study was to determine whether the combined data generated from the PetPace Collar and Actigraph Link accelerometer provide reliable pulse, respiration, and heart rate variability results during sedentary, light-moderate, and vigorous bouts in 11 freely moving dogs in a foster caretaker environment over 10⁻15 days. The second aim was to determine the effects of proximity (absence and presence of caretaker) and distance (caretaker and dog within 0⁻2 m) on the dogs’ physiological responses. Aim 1 results: Pulse and respiration were higher during light-moderate bouts compared to sedentary bouts, and higher at rest while the dogs were standing and sitting vs. lying. Heart rate variability (HRV) was not different between activity levels or position. Aim 2 results: During sedentary bouts, pulse and respiration were higher, and HRV lower, when there was a proximity signal (caretaker present) compared to no proximity signal (caretaker absent). Using multiple regression models, we found that activity, position, distance, and signal presence were predictors of physiological response in individual dogs during sedentary bouts. Our results suggest that combining data collected from Actigraph GT9X and PetPace monitors will provide useful information, both collectively and individually, on dogs’ physiological responses during activity, in various positions, and in proximity to their human caretaker

Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction

Mortality and morbidity were examined in 117 laboratory-maintained rhesus monkeys studied over approximately 25 years (8 dietary-restricted [DR] and 109 ad libitum-fed [AL] monkeys). During the study, 49 AL monkeys and 3 DR monkeys died. Compared with the DR monkeys, the AL monkeys had a 2.6-fold increased risk of death. Hyperinsulinemia led to a 3.7-fold increased risk of death ( p,.05); concordantly, the risk of death decreased by 7%, per unit increase in insulin sensitivity (M). There was significant organ pathology in the AL at death. The age at median survival in the AL was approximately 25 years compared with 32 years in the DR. The oldest monkey was a diabetic female (AL) that lived to be 40 years of age. These results suggest that dietary restriction leads to an increased average age of death in primates, associated with the prevention of hyperinsulinemia and the mitigation of age-related disease. THE morbidity and mortality rates for many humandiseases increases with age, leading investigators to examine the effects of aging on the onset and severity of human disease. However, successful gerontological inter-vention in age-related diseases has been complicated by the variation in the rate of aging processes across individual

Insulin Signaling and Insulin Sensitizing in Muscle and Liver of Obese Monkeys: Peroxisome Proliferator-Activated Receptor Gamma Agonist Improves Defective Activation of Atypical Protein Kinase C

Obesity, the metabolic syndrome, and aging share several pathogenic features in both humans and non-human primates, including insulin resistance and inflammation. Since muscle and liver are considered key integrators of metabolism, we sought to determine in biopsies from lean and obese aging rhesus monkeys the nature of defects in insulin activation and, further, the potential for mitigation of such defects by an in vivo insulin sensitizer, rosiglitazone, and a thiazolidinedione activator of the peroxisome proliferator-activated receptor gamma. The peroxisome proliferator-activated receptor gamma agonist reduced hyperinsulinemia, improved insulin sensitivity, lowered plasma triglycerides and free fatty acids, and increased plasma adiponectin. In muscle of obese monkeys, previously shown to exhibit defective insulin signaling, the insulin sensitizer improved insulin activation of atypical protein kinase C (aPKC), the defective direct activation of aPKC by phosphatidylinositol (PI)-3,4,5-(PO4)3, and 5′-AMP-activated protein kinase and increased carnitine palmitoyltransferase-1 mRNA expression, but it did not improve insulin activation of insulin receptor substrate (IRS)-1-dependent PI 3-kinase (IRS-1/PI3K), protein kinase B, or glycogen synthase. We found that, although insulin signaling was impaired in muscle, insulin activation of IRS-1/PI3K, IRS-2/PI3K, protein kinase B, and aPKC was largely intact in liver and that rosiglitazone improved insulin signaling to aPKC in muscle by improving responsiveness to PI-3,4,5-(PO4)3. Antioxid. Redox Signal. 14, 207–219

Leptin Augments the Acute Suppressive Effects of Insulin on Hepatic Very Low-Density Lipoprotein Production in Rats

It is well established that leptin increases the sensitivity of carbohydrate metabolism to the effects of insulin. Leptin and insulin also have potent effects on lipid metabolism. However, the effects of leptin on the regulation of liver lipid metabolism by insulin have not been investigated. The current study addressed the effects of leptin on insulin-regulated hepatic very low-density lipoprotein (VLDL) metabolism in vivo in rats. A 90-min hyperinsulinemic/euglycemic clamp (4 mU/kg · min−1) reduced plasma VLDL triglyceride (TG) by about 50% (P < 0.001 vs. saline control). Importantly, a leptin infusion (0.2 μg/kg · min−1) in combination with insulin reduced plasma VLDL-TG by about 80% (P < 0.001 vs. insulin alone). These effects did not require altered skeletal muscle lipoprotein lipase activity but did include differential effects of insulin and leptin on liver apolipoprotein (apo) B and TG metabolism. Thus, insulin decreased liver and plasma apoB100/B48 levels (∼50%, P < 0.01), increased liver TGs (∼20%, P < 0.05), and had no effect on fatty acid oxidation. Conversely, leptin decreased liver TGs (∼50%, P < 0.01) and increased fatty acid oxidation (∼50%, P < 0.01) but had no effects on liver or plasma apoB levels. Importantly, the TG-depleting and prooxidative effects of leptin were maintained in the presence of insulin. We conclude that leptin additively increases the suppressive effects of insulin on hepatic and systemic VLDL metabolism by stimulating depletion of liver TGs and increasing oxidative metabolism. The net effect of the combined actions of insulin and leptin is to decrease the production and TG content of VLDL particles