Biomedical subjects

K G Rowley

Publications and source records attributed to K G Rowley.

23 records · Page 2Linked to original sources

PubMed1996

Inositol hexakisphosphate binding sites in rat heart and brain.

1. Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and inositol hexakisphosphate (InsP6) are produced in response to stimulation of cardiac alpha 1-adrenoceptors. While the role of Ins(1,4,5)P3 and Ins(1,4,5)P3 receptors is well-defined in many tissues including brain, the functional role of the putative InsP6-InsP6 receptor system in cardiac function is less clear. Using quantitative autoradiography, this study examined the characteristics and regional localization of [3H]-InsP6 binding sites in rat heart and compared the affinity of a range of inositol polyphosphates for [3H]-InsP6 and [3H]-Ins(1,4,5)P3 binding sites in heart and brain. 2. [3H]-InsP6 bound to a single, high affinity site in sections of rat heart (KD ranging from 22 +/- 1.9 nM in right atria to 35 +/- 2.6 nM in the interventricular septum, n = 7). The maximal number of binding sites (Bmax) ranged from 5.1 +/- 0.48 to 12 +/- 1.8 pmol mg-1 protein in left atrium and left ventricle, respectively. Inositol phosphates inhibited binding of [3H]-InsP6 with the order of potency: InsP6 > Ins(1,4,5)PS3 > inositol 1,3,4,5-tetrakisphosphate > or = inositol pentakisphosphate > Ins(1,4,5)P3 > > inositol mono- and bisphosphates, consistent with the labelling of an InsP6 binding site. 3. The Ins(1,4,5)P3 analogue, Ins(1,4,5)PS3, originally investigated as a putative selective radioligand for the Ins(1,4,5)P3 receptor, was a potent inhibitor of [3H]-InsP6 binding in all heart regions (K1 = 170-260 nM). The K1 of Ins(1,4,5)PS3 for the inhibition of [3H]-Ins(1,4,5)P3 binding in rat brain (60-220 nM) was similar to that observed for the inhibition of [3H]-InsP6 binding in heart, suggesting that Ins(1,4,5)PS3 is not a specific ligand for either Ins(1,4,5)P3 or InsP6 receptor binding sites. 4. Previous studies have detected [3H]-InsP6 binding in mitochondrial and sarcoplasmic reticulum fractions of heart and links between InsP6 and cardiac mitochondrial Ca2+ regulation have been proposed, suggesting further studies are warranted to determine the functional role(s) of InsP6 and InsP6 receptor binding sites in cardiac tissue.

Animals↗

PubMed1996

Abnormal glucose tolerance and other coronary heart disease risk factors in an isolated aboriginal community in central Australia.

OBJECTIVE: To determine the age- and sex-specific prevalence of diabetes, impaired glucose tolerance (IGT), and coronary heart disease risk factors in a remote central Australian Aboriginal community maintaining some degree of traditional lifestyle, living in homeland communities on their ancestral land. RESEARCH DESIGN AND METHODS: A cross-sectional survey of 437 subjects > or = 15 years of age (189 men, 248 women), representing 80% of the adult population residing in the community at the time of the survey, was performed and the following parameters measured: BMI, glucose tolerance, circulating insulin and lipids, and blood pressure. RESULTS: The mean BMI for this population was 22.9 +/- 4.8 kg/m2. The prevalence of diabetes in the age group of 15-34 years (103 men and 140 women) was 2 and 6% for men and women, respectively. In the 35-years-and-older age group (86 men and 108 women), diabetes prevalence was 19 and 13% for men and women, respectively. Over half the diabetic subjects did not exhibit fasting hyperglycemia. IGT occurred in 8 and 15% of younger men and women, respectively, and in 17 and 32% of older men and women, respectively. Smoking was common among men (53% current smokers) but rare among women (2% current smokers). The prevalence of hypercholesterolemia, hypertriglyceridemia, hypertension, and overweight rose with increasing degrees of glucose intolerance. The two communities adjacent to the only store in the area had a higher prevalence of abnormal glucose tolerance than did the more remote homeland communities (odds ratio for abnormal glucose tolerance: 2.92; 95% CI 1.51-5.63). CONCLUSIONS: Despite their relative leanness, this Aboriginal population exhibited relatively high prevalences of IGT and diabetes without fasting hyperglycemia. The data suggest a protective effect of a decentralized mode of living, as opposed to a more urbanized lifestyle, on the occurrence of glucose intolerance. Abnormal lipid profiles (particularly high triglycerides and low HDL cholesterol) and the high prevalence of smoking in men indicated a high-risk profile for coronary heart disease in this population.

Adolescent↗

PubMed1991

Altered alpha 1-adrenoceptor-mediated responses in atria of rats with chronic left ventricular infarction.

Phosphoinositide (PI) turnover, chronotropic and inotropic responses to alpha 1-adrenoceptor activation, and alpha 1-adrenoceptor density were studied in atria from rats with left ventricular myocardial infarction (LVMI) and noninfarcted rats. LVMI was produced after surgical ligation of the left coronary artery in 8-week-old Wistar rats. Rats were killed 4 weeks after this operation when rats with LVMI had developed significant hypertrophy of both ventricles and atria. Phenylephrine 0.1 mM to 1 mM, with propranolol 0.3 mM, produced a concentration-dependent increase in heart rate (HR) in right atria from noninfarcted rat hearts, and this response was significantly reduced in rats with LVMI. In electrically driven left atria, the concentration-dependent, phenylephrine-induced positive inotropic responses observed with propranolol added were also significantly impaired in rats with LVMI as compared with those of noninfarcted rats. In contrast, neither PI turnover in response to phenylephrine in the presence of propranolol nor alpha 1-adrenoceptor density was reduced in rats with LVMI. These results suggest that the impaired alpha 1-adrenoceptor-induced chronotropic and inotropic responses in atria from rats with LVMI are not due to downregulation of alpha 1-adrenoceptors or to impaired activation of PI turnover after alpha 1-adrenoceptor stimulation, but to impairment of one or more biochemical responses distal to PI hydrolysis or changes in coupling mechanisms other than hydrolysis of PIs.

Animals↗

PubMedDate not supplied

Insulin resistance syndrome in Australian aboriginal people.

1. Like many indigenous populations, Australian Aboriginal people have developed high rates of obesity, non-insulin-dependent diabetes mellitus (NIDDM) and cardiovascular and renal disease following the transition from a traditional to an 'urbanized' lifestyle. These conditions tend to cluster as part of the insulin resistance syndrome. 2. The prevalence of overweight people and obesity in Australian Aboriginal populations ranges from 0% in communities with a traditionally orientated lifestyle to well over 50% in the worst affected communities. There is a predominantly central pattern of fat deposition in both men and women, which is associated with greater insulin resistance and cardiovascular risk than is peripheral fat deposition. 3. Data from four previously published, population-based surveys in Aboriginal communities were combined to give a cohort of 1079 subjects of 15 years and older. Several conditions of the insulin resistance syndrome had a strong, positive association with increasing body mass index (BMI): NIDDM (both cross-sectionally and longitudinally), hypertension, dyslipidaemia and albuminuria. Remaining lean (BMI < 20 kg/m2) protected even older Aboriginal people from these conditions to a large extent. 4. Community based programmes to increase physical activity and improve dietary quality are likely to be the major means by which conditions associated with insulin resistance can be prevented in Aboriginal populations.

Female↗

PubMedDate not supplied

Diabetes in Australian aboriginal and Torres Strait Islander peoples.

Type 2 diabetes arises from a complex and multifactorial set of factors, including genetic susceptibility, behaviour (including diet and exercise), early nutrition, obesity and psychosocial stress, leading to insulin resistance and pancreatic failure. These factors in turn are influenced by social and physical environmental factors. Each of these may be important determinants of the high prevalence and incidence of type 2 diabetes in Australian Aboriginal and Torres Strait Islander people. Public health interventions for primary and secondary prevention need to recognize this complexity. Although a reduction in the prevalence of obesity or diabetes in the short-medium term is rarely if ever achieved, there are documented examples of community-based programs which have been effective in reducing the risk of developing type 2 diabetes and its cardiovascular complications. Such interventions need to be community-directed and appropriate to local circumstances in order to be effective.

Australia↗