Insulin-like growth factor-1 stimulation of cells induces formation of complexes containing phosphatidylinositol-3-kinase, guanosine triphosphatase-activating protein (GAP), and p62 GAP-associated protein.

The insulin-like growth factor-1 (IGF-1) receptor is structurally related to the insulin receptor and shares common features in receptor signaling. These features include receptor autophosphorylation, phosphorylation of insulin receptor substrate-1, and activation of Ras and phosphatidylinositol-3-kinase (PI3K). Previously, we reported that after insulin treatment of rat HTC cells expressing human insulin receptors, a unique insulin receptor signaling complex was formed that contained the insulin receptor, the p85 subunit of PI3K, GTPase-activating protein (GAP), and p62 GAP-associated protein. In the present study, using wild type HTC cells, we investigated whether the activated IGF-1 receptor also forms a similar signaling complex. To study the proteins present in IGF-1 receptor signaling complexes, we used immunoprecipitation and Western blotting analysis with appropriate antibodies. In response to IGF-1, insulin receptor substrate-1 was tyrosine phosphorylated and formed a complex with the PI3K heterodimer that consists of a p85 regulatory subunit and a p110 catalytic subunit. In addition, a separate complex was formed, consisting of p85, p62 GAP-associated protein and GAP. The p62 in this complex was tyrosine phosphorylated. These studies suggest, therefore, that the IGF-1 receptor, like the insulin receptor, induces the formation of multiple signaling complexes that most likely mediate the proliferative effects of these receptors.

Relation of plasma lipids to insulin resistance, nonesterified fatty acid levels, and body fat in men from three ethnic groups: relevance to variation in risk of diabetes and coronary disease.

Afro-Caribbean men in the United Kingdom have a favorable lipoprotein profile and are at low risk of coronary heart disease (CHD) compared with Europeans and South Asians, but are at high risk of non-insulin-dependent diabetes mellitus (NIDDM) compared with Europeans. To investigate these differences, a cross-sectional comparison was undertaken for measures of lipoprotein metabolism, body composition, and insulin's glucoregulatory and antilipolytic actions in 92 healthy men (42 to 61 years) of Afro-Caribbean, South Asian, or European origin. Afro-Caribbean men were more insulin-resistant than Europeans (insulin sensitivity [Si], 1.96 v3.01 min(-1) x microU(-1) x mL, P < .01). They nevertheless had a more favorable lipoprotein profile, with lower levels of very-low-density lipoprotein (VLDL) cholesterol (0.21 v 0.40 mmol/L, P < .01) and triglycerides (0.34 v 0.74 mmol/L, P < .01), lower serum total triglycerides, higher high-density lipoprotein 2 (HDL2) cholesterol, and larger low-density lipoprotein (LDL) particle size. These differences were not accounted for by differences in nonesterified fatty acid (NEFA) levels, the sensitivity of suppression of NEFA levels to insulin, or body composition. South Asians were also more insulin-resistant than Europeans but had a less favorable lipoprotein profile. Afro-Caribbean men in the United Kingdom are as insulin-resistant as South Asian men but less susceptible to the lipid disturbances that characteristically accompany insulin resistance. This favorable lipid pattern may relate to more effective VLDL metabolism rather than a reduced supply of NEFA as substrate for triglyceride synthesis.

Intracranial haemorrhage in patients on antithrombotics: clinical presentation and determinants of outcome in a prospective multicentric study in Italian emergency departments.

BACKGROUND: Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). METHODS: Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. RESULTS: We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8 and 19.4%, respectively, while < 30% underwent procoagulant medical treatment. At the 3-month follow-up, the case fatality rate was 42.0%, while disability or death (MRS 3-6) was 68.1%. The odds ratio for death in OA versus AP patients was 2.63 (95% CI 1.73-4.00) in the whole population and 2.80 (95% CI 1.77-4.41) in intraparenchymal event patients. Glasgow Coma Scale, age, spontaneous event and anticoagulant use were found to be predictors of death both in traumatic and spontaneous events. CONCLUSION: This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.

A review on ethnic differences in plasma triglycerides and high-density-lipoprotein cholesterol: is the lipid pattern the key factor for the low coronary heart disease rate in people of African origin?

Black people in the UK, in the Caribbean, and to a lesser extent in the USA, experience coronary heart disease events at different rates than white people. Despite having higher prevalence of hypertension, cigarette smoking and diabetes, black males have significantly lower coronary heart disease rates than white males, whereas no significant differences have been detected in females. The only known risk factor differences that could account for the difference in CHD rates are higher HDL cholesterol and lower triglycerides that are seen in blacks compared with whites. Obesity and, in particular abdominal obesity, seems to determine TG and HDL cholesterol levels: black males are less centrally obese than whites, while total adiposity and central distribution of fat is more predominant in black females compared with white females. We propose that the less degree of abdominal adiposity observed in black males is related with an increased anti-lipolytic effect of insulin, which could account for low triglycerides and high HDL cholesterol levels, and consequently explain the higher protection from coronary heart disease experienced by black males compared with whites and black females.