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Y Liang

Publications and source records attributed to Y Liang.

At least 343 records · Page 19Linked to original sources
PubMed1994

Mechanisms of action of nonglucose insulin secretagogues.

Insulin release induced by nonglucose secretagogues is initiated from beta-cell by a wide variety of stimuli through specific receptors or binding sites. Activation of receptors in turn generates or enhances the cytosol levels of cAMP, cADPR, IP3, DAG, and AA. These second messengers then activate protein kinases, change the ion currents cross the cell membrane, and mobilize intracellular Ca2+, thereby increasing phosphorylated proteins in the cytosol and augmenting [Ca2+]i. These events trigger exocytotic discharge of insulin. The crucial steps in receptor-mediated stimulation-secretion coupling and their relationship to glucose-stimulated insulin release is summarized in Figure 1. At the present stage of research, the general processes of secretagogue binding to receptors, of generating second messengers, of activating several types of protein kinase, and of altering the membrane potential as well as cytosol calcium levels has been intensively studied and qualitatively clarified. However, we know little about the exact nature of substrates of different protein kinases and their function in the insulin secretion process. With the help of molecular biology and protein chemistry, we expect that this gap will be filled in the near future.

Adenylyl Cyclases↗
PubMed1994

In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents.

The present study evaluated the involvement of glucose transport and phosphorylation in glucose-stimulated insulin release from pancreatic islets. Using quantitative histochemical techniques, we investigated basal islet glucose content, islet glucose uptake in situ during acute extreme experimental hyperglycemia, and islet glucokinase activity in several animal models of diabetes and obesity. The basal islet glucose content in anaesthetized diabetic or obese rodents was either the same or higher than that in their relevant controls. The rate of glucose uptake of islet tissue in these animals after an i.v. glucose injection was different. The db+/db+ mouse and the obese Zucker rat exhibited significantly reduced islet glucose uptake rates. RIP-cHras transgenic mice, BHE/cdb rats and partially pancreatectomized rats showed normal islet glucose uptake rates. The activity of islet glucokinase was increased to a different degree related to the blood glucose level. All five animal models of diabetes or obesity exhibited either a delay or a reduction of insulin release in response to supra maximal glucose stimulation. Our results indicate that the impairment of glucose-induced insulin release in diabetes is not consistently associated with a reduction of islet glucose uptake nor a change of glucokinase activity.

Animals↗
PubMed1994

Effects of glucose on insulin secretion, glucokinase activity, and transgene expression in transgenic mouse islets containing an upstream glucokinase promoter-human growth hormone fusion gene.

We have analyzed in organ culture the effects of glucose on glucose-induced insulin secretion, glucokinase (GK) activity, and human growth hormone (hGH) expression in pancreatic islets from transgenic mice containing an upstream GK promoter-hGH fusion gene. Freshly isolated islets from these mice had a normal insulin secretory response to glucose but showed subtle defects after culture in low or high glucose for 4 days that may have been due to the accumulation of hGH in the culture media. Islets cultured from both normal and transgenic mice had approximately a fourfold induction of GK activity in response to an increased concentration of glucose in the culture media, whereas no such change in total islet hGH production was observed. Immunocytochemical localization of hGH in islets cultured in 3 mM glucose showed a pattern similar to that in freshly isolated islets. However, after culture in 30 mM glucose, hGH immunostaining became strikingly more heterogeneous. We conclude 1) that GK-hGH transgene expression does not appear to adversely affect glucose-stimulated insulin secretion in vivo or in freshly isolated islets, 2) that glucose does not induce transgene expression, thus providing additional evidence against an effect of glucose on GK gene transcription in the islet, and 3) that glucose stimulates the co-release of hGH with insulin, thereby enhancing the heterogeneous staining pattern seen among pancreatic beta-cells.

Animals↗
PubMed1994

Machado-Joseph disease in pedigrees of Azorean descent is linked to chromosome 14.

A locus for Machado-Joseph disease (MJD) has recently been mapped to a 30-cM region of chromosome 14q in five pedigrees of Japanese descent. MJD is a clinically pleomorphic neurodegenerative disease that was originally described in subjects of Azorean descent. In light of the nonallelic heterogeneity in other inherited spinocerebellar ataxias, we were interested to determine if the MJD phenotype in Japanese and Azorean pedigrees arose from mutations at the same locus. We provide evidence that MJD in five pedigrees of Azorean descent is also linked to chromosome 14q in an 18-cM region between the markers D14S67 and AACT (multipoint lod score +7.00 near D14S81). We also report molecular evidence for homozygosity at the MJD locus in an MJD-affected subject with severe, early-onset symptoms. These observations confirm the initial report of linkage of MJD to chromosome 14; suggest that MJD in Japanese and Azorean subjects may represent allelic or identical mutations at the same locus; and provide one possible explanation (MJD gene dosage) for the observed phenotypic heterogeneity in this disease.

Age of Onset↗
PubMed1994

Cerebellar infarction. Analysis of 22 cases.

Twenty-two cases of cerebellar infarction were diagnosed by clinical findings, computerized tomography (CT), magnetic resonance image (MRI) and autopsy. Most of the infarctions occurred in the territory of the posterior inferior cerebellar artery (18/22). The most common and earliest symptoms were dizziness or vertigo (19/22), which occurred repeatedly and were accompanied by nausea and vomiting. The symptoms and signs of cerebellar lesion such as unsteady gait, limb and/or trunk ataxia, dysarthria were also the main clinical manifestations. However, in a number of patients there were no cerebellar symptoms or signs (9/22). Rapid deterioration of consciousness suggested acute compression of the brainstem, where the prognosis would be poor. CT scan made it possible to diagnose cerebellar infarction in the patients. But CT is not a satisfactory instrument in identifying this disease. MRI without bony artifacts from the posterior fossa has much higher resolution and renders the infarction to be visualized earlier. It may be regarded as the most ideal instrument in diagnosing this disease.

Adult↗
PubMed1993

Mutation of the gene for the human lysosomal serine protease cathepsin G is not the cause of aberrant APP processing in familial Alzheimer disease.

Recent genetic linkage studies have implicated a gene on chromosome 14 in the pathogenesis of FAD. The identity of this gene remains unknown but it has been speculated that it may be involved in the cellular processing of the amyloid precursor protein (APP). We have analyzed the nucleotide sequence of the entire open reading frame of the cathepsin G gene located on chromosome 14q. No mutations were observed, suggesting that defects in this lysosomal protease are not responsible for aberrant accumulation of proteolytic products of APP in FAD brain tissue.

Alzheimer Disease↗
PubMed1993

Effects of diethyl spermine analogues in human bladder cancer cell lines in culture.

The biochemical and antiproliferative effects of two recently developed N-alkylated analogues of naturally-occurring polyamines, N1,N14-diethylhomospermine (DEHSPM) and N1,N11-diethylnorspermine (DENSPM), were investigated in two human transitional cell carcinoma (TCC) lines, T24 and J82. Parallel studies with the ornithine decarboxylase enzyme inhibitor alpha-difluoromethylornithine (DFMO) were included for comparison. DENSPM displayed greater antiproliferative activity than DEHSPM in both TCC cell lines. Both analogues were strikingly more potent than DFMO. DEHSPM and DENSPM suppressed the activity of the major biosynthetic enzymes, ornithine decarboxylase and S-adenosylmethionine decarboxylase. However, differences in the resulting polyamine depletion suggest that the substantial antiproliferative activity of these analogues may result from mechanisms other than polyamine depletion. The greater polyamine depletion seen with DENSPM is thought to result from its striking induction of spermidine/spermine N1-acetyltransferase. DENSPM is an attractive agent for further preclinical and clinical development, possibly as a chemopreventive agent, in TCC of the bladder.

Carcinoma, Transitional Cell↗