Role of protein kinase C isoenzymes in fatty acid stimulation of insulin secretion.

Although hyperlipidemia is frequently associated with hyperinsulinemia. the stimulation of insulin secretion by fatty acids in the in vitro studies has remained a matter of constant debate, partly because of the uncertainty about a clearly defined mechanism to explain such a direct effect. In this study, we used a pharmacologic approach to test the hypothesis that protein kinase C (PKC) signal-transduction pathway is involved in fatty acid-stimulated insulin secretion. Isolated rat islets were perifused with either palmitate (C(16:0)) or linoleate (C(18:2)) in the absence or presence of selective inhibitors of PKC isoenzymes. Our results suggest a role for Ca2+-independent PKC isoenzymes in the signal transduction of fatty acid-stimulated insulin secretion. The data imply that either the nonconventional and/or atypical isoforms of PKC are involved in the stimulation of insulin release induced by fatty acids.

Vitamin B12 status in hospitalized elderly from nursing homes and the community.

OBJECTIVE: To assess vitamin B(12) status in a large sample of hospitalized, inner-city older adults from nursing homes and communities with low socioeconomic status. To determine additionally if hypoalbuminemia can help identify older subjects who are at risk for vitamin B(12) deficiency. DESIGN: A cross-sectional study of hospitalized, inner-city older residents. SETTING: Acute Care Geriatrics Division, a 75-bed inpatient care service at Our Lady of Mercy Medical Center (OLMMC), a University Affiliate of New York Medical College. PARTICIPANTS: A total of 466 older patients (aged 65 to 102 years) from the community (n = 374) and nursing homes (n = 92) who were admitted to the acute care geriatrics division from 1993 to 1996. MEASUREMENTS: Patients admitted to the hospital had serum vitamin B(12) and albumin levels determined along with other nutritional parameters, routine blood tests, and physical examinations. RESULTS: On admission, 19% of hospitalized subjects had marginal serum B(12) levels (200-350 pg/mL) and 6% had low serum B(12) levels (<200 pg/mL). Mean serum B(12) levels did not differ significantly between patients from nursing homes and those from the community. Sixty-four percent 64% of all patients had low serum albumin levels (alb < 3.5 g/dL), with patients from nursing homes showing significantly lower mean serum albumin than patients admitted from the community (P <.000). We observed no positive correlation between serum albumin and serum vitamin B(12) in our older hospitalized patients from either nursing homes or community. CONCLUSIONS: In this sample of hospitalized older adults, 24% were found to have marginal or low serum B(12) status. Thus, we believe that periodic determinations of serum B(12) would be a useful addition to the general health and nutritional assessment in this age group. Our findings also suggest that hypoalbuminemia is not helpful as a predictor of low B(12) status in older hospitalized persons.

Current status of antioxidant therapy for Alzheimer's Disease.

Accumulating evidence from preclinical and clinical studies supports the hypothesis that oxidative stress may be associated with the onset and progression of Alzheimer's Disease (AD). Antioxidant therapies are being promoted in the lay press to enhance mental functions and delay cognitive losses with aging. An increasing number of physicians are also recommending antioxidant therapies, such as high dose vitamin E, for subjects with AD and other neurodegenerative disorders. High dose vitamin E, ginkgo biloba, and selegiline are three putative antioxidants that have been tested in randomized multicenter trial conditions in the US. This paper summarizes the oxidative stress hypothesis of AD and reviews the strengths and limitations of published antioxidant studies in AD in relation to the role of such therapies in practice.

Early recognition of Alzheimer's disease: what is consensual? What is controversial? What is practical?

Alzheimer's disease is often unrecognized or misdiagnosed in its early stages. Despite the lack of curative treatments, there are compelling reasons why early recognition of Alzheimer's disease may offer substantial benefits. Early evaluation and diagnosis may offer opportunities to enhance patient safety, allow families to plan for the future, provide family education and support, and initiate the best treatment before more substantial neuronal loss occurs. Barriers to early diagnosis include failure of family or physicians to recognize the existence or importance of cognitive/functional changes and/or misperceptions regarding diagnostic requirements and treatment capabilities. There is consensus that high diagnostic accuracy can be achieved clinically, even by nonspecialists, using established criteria and practice parameters. Population-based screening programs for the elderly, genetic testing, yield of routine neuroimaging studies, and the diagnostic value of certain molecular markers remain controversial. This review highlights practical issues related to the initial clinical evaluation and differential diagnosis of Alzheimer's disease.

Reoxygenation injury affects isolated islet response to fatty acid stimulation.

Hyperlipidemia is frequently associated with hyperinsulinemia, but because the effects of fatty acids on insulin secretion in in vitro studies using isolated perifused islets have mostly been described with supraphysiological concentrations of fatty acids, it has remained uncertain whether elevated lipid levels contribute to hyperinsulinemia by their direct stimulation of insulin secretion. In the present study, we have identified reoxygenation injury in isolated islet function as a contributing factor in the failure of physiological concentrations of free fatty acids to stimulate insulin secretion in isolated perifused islets. Reoxygenation of isolated islets is associated with the production of reactive oxygen species, which impair islet function. We have found that pretreatment of freshly isolated islets with the antioxidant glutathione (GSH), as well as a 24-hour preculture of isolated islets under appropriate conditions, enhanced their sensitivity to fatty acid stimulation.