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While a potential causal factor in Alzheimer's disease (AD), brain insulin resistance has not been demonstrated directly in that disorder. We provide such a demonstration here by showing that the hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in(More)
A frontal variant of Alzheimer's disease (AD) has recently been identified on neuropathological and neuropsychological grounds (Johnson, J.K., Head, E., Kim, R., Starr, A., Cotman, C.W., 1999. Clinical and pathological evidence for a frontal variant of Alzheimer Disease. Arch. Neurol. 56, 1233-1239). Frontal AD differs strikingly from typical AD by the(More)
Ethylene glycol poisoning is an important toxicological problem in medical practice because early diagnosis and treatment can prevent considerable morbidity and mortality. When ingested in the form of antifreeze or other automotive products, ethylene glycol results in central nervous system depression, cardiopulmonary compromise, and renal insufficiency.(More)
Previous studies have demonstrated that myo-inositol 1,4,5-trisphosphate (IP3) mobilizes Ca2+ from the endoplasmic reticulum (ER) of digitonin-permeabilized islets and that an increase in intracellular free Ca2+ stimulates insulin release. Furthermore, glucose stimulates arachidonic acid metabolism in islets. In digitonin-permeabilized islets, exogenous(More)
The present experiments were undertaken to examine the hypothesis that glucose-induced increased de novo synthesis of 1,2-diacyl-sn-glycerol (which has been observed in a number of different tissues, including retinal capillary endothelial cells exposed to elevated glucose levels in vitro) and associated activation of protein kinase C may play a role in(More)
Thyrotropin-releasing hormone (TRH) is present in small quantities in the rat adult pancreas. As hypothyroidism increases dramatically the pancreatic content of this peptide, this model was used to localize TRH in the gland by immunocytochemistry. Immunocytochemical staining of semithin (0.5-1.0 micron) and thin (golden) sections was performed as well as(More)
Synaptotagmins (Syt) play important roles in Ca(2+)-induced neuroexocytosis. Insulin secretion of the pancreatic beta-cell is dependent on an increase in intracellular Ca(2+); however, Syt involvement in insulin exocytosis is poorly understood. Reverse transcriptase-polymerase chain reaction studies showed the presence of Syt isoforms III, IV, V, and VII in(More)
In the beta TC3 insulin-secreting beta-cell line, glucose rapidly induces the tyrosine phosphorylation of the 97-kDa insulin receptor beta-subunit. Phosphorylation is transient, with fourfold stimulation by 2 min and subsequent dephosphorylation to basal levels by 10-15 min. Elevating the extracellular KCl concentration equipotently initiates receptor(More)
Carnitine-deficiency syndromes are often associated with alterations in lipid metabolism and cardiac function. The present study was designed to determine whether this is also seen in an experimental model of carnitine deficiency. Carnitine deficiency was induced in male Sprague-Dawley rats supplemented with sodium pivalate for 26 to 28 weeks. This(More)
Recombinant human interleukin 1 alpha (IL-1) has been found to induce prostaglandin E2 (PGE2) accumulation by isolated rat islets of Langerhans at concentrations similar to those at which the cytokine inhibits glucose-induced insulin secretion and islet glucose oxidation. Maximal stimulation of PGE2 accumulation (5 times control value) occurred at 200 pM(More)