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51.
Renu Bala Puri Kawluru Anjaneyulu Jalil R. Kidwai Varanasi K. Mohan Rao 《Acta diabetologica》1978,15(5-6):243-250
Summary Cathepsin B, purified from isolated islets of Langerhans, when incubated with proinsulin underin vitro conditions could convert proinsulin to insulin and C-peptide, releasing free arginine and lysine. When C-peptide, prepared
from rat pancreas, was added to the incubation system consisting of proinsulin and cathepsin B, it completely inhibited the
conversion of proinsulin to insulin.
Communication no. 2295 from the Central Drug Research Institute, Lucknow, India. 相似文献
52.
Anjaneyulu Dirisala Kensuke Osada Qixian Chen Theofilus A. Tockary Kaori Machitani Shigehito Osawa Xueying Liu Takehiko Ishii Kanjiro Miyata Makoto Oba Satoshi Uchida Keiji Itaka Kazunori Kataoka 《Biomaterials》2014
Poly(ethylene glycol) (PEG) modification onto a gene delivery carrier for systemic application results in a trade-off between prolonged blood circulation and promoted transfection because high PEG shielding is advantageous in prolonging blood retention, while it is disadvantageous with regard to obtaining efficient transfection owing to hampered cellular uptake. To tackle this challenging issue, the present investigation focused on the structure of polyplex micelles (PMs) obtained from PEG–poly(l-lysine) (PEG–PLys) block copolymers characterized as rod-shaped structures to seek the most appreciable formulation. Comprehensive investigations conducted with particular focus on stability, PEG crowdedness, and rod length, controlled by varying PLys segment length, clarified the effect of these structural features, with particular emphasis on rod length as a critical parameter in promoting cellular uptake. PMs with rod length regulated below the critical threshold length of 200 nm fully exploited the benefits of cross-linking and the cyclic RGD ligand, consequently, exhibiting remarkable transfection efficiency comparable with that of ExGen 500 and Lipofectamine® LTX with PLUS™ even though PMs were PEG shielded. The identified PMs exhibited significant antitumor efficacy in systemic treatment of pancreatic adenocarcinoma, whereas PMs with rod length above 200 nm exhibited negligible antitumor efficacy despite a superior blood circulation property, thereby highlighting the significance of controlling the rod length of PMs to promote gene transduction. 相似文献
53.
Several lines of recent evidence implicate regulatory roles for reactive oxygen species (ROS) in islet function and insulin secretion. The phagocyte-like NADPH oxidase (Nox2) has recently been shown to be one of the sources of ROS in the signaling events leading to glucose stimulated insulin secretion (GSIS). We recently reported inhibition of glucose- or mitochondrial fuel-induced Nox2-derived ROS by a specific inhibitor of protein farnesyl transferse (FTase; FTI-277), suggesting that activation of FTase might represent one of the upstream signaling events to Nox2 activation. Furthermore, FTase inhibitors (FTI-277 and FTI-2628) have also been shown to attenuate GSIS in INS 832/13 cells and normal rodent islets. Herein, we provide further evidence to suggest that inhibition of FTase either by pharmacological (e.g., FTI-277) or gene silencing (siRNA-FTase) approaches markedly attenuates mitochondrial fuel-stimulated insulin secretion (MSIS) in INS 832/13 cells. Together, our findings further establish a link between nutrient-induced Nox2 activation, ROS generation and insulin secretion in the pancreatic β-cell. 相似文献
54.
55.
Erythrocyte sodium-potassium ATPase activity and thiol metabolism in genetically hyperglycemic mice.
Erythrocyte sodium pump activity, osmotic fragility, and thiol status were measured in genetically hyperglycemic (db/db) mice and compared with their nondiabetic littermates (db/m). The data showed no major differences in these parameters. However, erythrocytes from streptozotocin (Stz)-induced diabetic rats had significantly lower activity of sodium pump and thiols with an almost fourfold increase in osmotic fragility as compared with erythrocytes from nondiabetic rats. Sorbinil (an aldose reductase inhibitor) treatment of Stz-diabetic rats normalized all these lesions, suggesting a key role for polyol pathway. However, sorbitol levels in erythrocytes from db/db and db/m mice were undetectable. The data suggest that in db/db mice, the relative lack of polyol pathway, a potential consumer of NADPH, may provide erythrocytes with optimal NADPH for glutathione reductase system, thus maintaining normal GSH levels even at the height of hyperglycemia. Thus, the genetically hyperglycemic mice may serve as a useful model to study diabetes related complications without involving polyol pathway. 相似文献
56.
Lipopolysaccharide (LPS), a major constituent of the outer membrane of the cell wall of gram‐negative bacteria, is known to cause inflammatory pain. Quercetin, a dietary flavonoid, is claimed to have antiinflammatory activity in a few experimental studies. However, it is not known whether quercetin can reverse the hyperalgesia that is secondary to the inflammation. The aim of the present study was to evaluate the effect of quercetin on LPS‐induced alteration of pain perception in mice. Central perception of pain was assessed with the tail‐flick and hot plate methods and behavioural hyperalgesia was assessed by noting the animal's reactions such as redness, paw licking, and rearing after the intraplantar injection of LPS (10 μg/paw). Local administration of LPS induced significant hyperalgesia when measured by both central effects and behavioural reactions. Quercetin (50 and 100 mg/kg), like dexamethasone (0.5 mg/kg), attenuated central and behavioural hyperalgesia. This effect of quercetin was sensitive to reversal by naloxone (2 mg/kg). Our results thus indicate that quercetin protects against LPS‐induced hyperalgesia through modulation of the opioidergic system. Drug Dev. Res. 58:248–252, 2003. © 2003 Wiley‐Liss, Inc. 相似文献
57.
A semi-synthetic 1-0-alkyl-2-acetyl--glycero-3-phosphocholine (alkylacetyl-GPC) was shown to be highly species selective in its capacity to cause platelet aggregation and serotonin release. No effects were elicited on the rat or mouse platelets while platelets from human, dog, cat, rabbit, guinea pig and horse were highly sensitive to alkylacetyl-GPC. The hypotensive activity in the rat was not associated with thrombocytopenia. Preliminary evidence suggested that the inability of platelets of the rat and mouse to respond to alkylacetyl-GPC was not due to a difference in plasma inactivation of the substance but due to a difference in platelet responsiveness . The data also support the concept that the potent hypotensive property of this substance readily observed in the rat, is a result of an effect which is platelet-independent. 相似文献
58.
Anjaneyulu AS Rao VL Sastry VG Rao DV 《Journal of Asian natural products research》2008,10(7-8):597-601
A novel rearranged sesquiterpenoid, trocheliophorin (1) has been isolated from the soft coral Sarcophyton trocheliophorum besides the known compounds, sarcophytin, methyl arachidonate, and two polyhydroxy steroids (24S)-24-methylcholestane-3beta,5alpha,6beta,25-tetrol-25-monoacetate and (24S)-24-methylcholestane-3beta,5alpha,6beta,25-tetrol. The structure of the new sesquiterpenoid was elucidated by a study of its spectral data. 相似文献
59.
Free fatty acids regulate insulin secretion through metabolic and intracellular signaling mechanisms such as induction of malonyl-CoA/long-chain CoA pathway, production of lipids, GPRs (G protein-coupled receptors) activation and the modulation of calcium currents. Fatty acids (FA) are also important inducers of ROS (reactive oxygen species) production in β-cells. Production of ROS for short periods is associated with an increase in GSIS (glucose-stimulated insulin secretion), but excessive or sustained production of ROS is negatively correlated with the insulin secretory process. Several mechanisms for FA modulation of ROS production by pancreatic β-cells have been proposed, such as the control of mitochondrial complexes and electron transport, induction of uncoupling proteins, NADPH oxidase activation, interaction with the renin-angiotensin system, and modulation of the antioxidant defense system. The major sites of superoxide production within mitochondria derive from complexes I and III. The amphiphilic nature of FA favors their incorporation into mitochondrial membranes, altering the membrane fluidity and facilitating the electron leak. The extra-mitochondrial ROS production induced by FA through the NADPH oxidase complex is also an important source of these species in β-cells. 相似文献
60.
The protein phosphatase 2A [PP2A] family of enzymes has been implicated in the regulation of a variety of cellular functions including hormone secretion, growth, survival and apoptosis. PP2A accounts for ~1% of total cellular protein and ~ 80% of total serine/threonine phosphatases, thus representing a major class of protein phosphatases in mammalian cells. Despite significant advances in our current understanding of regulation of cellular function by PP2A under physiological conditions, little is understood with regard to its regulation under various pathological conditions, such as diabetes. Emerging evidence suggests hyperactivation of PP2A in liver, muscle, retina and the pancreatic islet under the duress of glucolipotoxicity and diabetes. Interestingly, pharmacological inhibition of PP2A or siRNA-mediated depletion of the catalytic subunit of PP2A [PP2Ac] levels largely restored PP2A activity to near normal levels under these conditions. Herein, we provide an overview of PP2A subunit expression and activity in in vitro and in vivo models of glucolipotoxicity and diabetes, and revisit the existing data, which are suggestive of alterations in post-translational methylation, phosphorylation and nitration of PP2Ac under these conditions. Potential significance of hyperactive PP2A in the context of cell function, survival and apoptosis is also highlighted. It is hoped that this commentary will provide a basis for future studies to explore the potential for PP2Ac as a therapeutic target for the treatment of diabetes and other metabolic disorders. 相似文献