ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system. 相似文献
1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path.
2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10?mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method.
3. The study observes that CGA is rapidly absorbed in plasma with tmax of 1?min similar to IV route after IN administration. The peak plasma concentration and AUC0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route.
4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360?min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUCbrain, IN) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUCbrain, IV) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders. 相似文献
Summary The effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10–9–10–6 mol/l, which corresponds to concentrations found in the plasm of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect.
Send offprint requests to O. Binah at the above address 相似文献
Membrane order was measured in the erythrocyte ghost membranes of DSM-III schizophreniform disorder (SF), DSM-III schizophrenic (SCZ) and DSM-III manic (bipolar) (M) patients and a group of age- and sex-matched controls. Fluorescence polarization with the probe 1,6-diphenyl1-1,3,5-hexatriene was used to determine the steady-state fluorescence anisotropy (rs). The SF group showed a significant increase in rs (Δrs = 0.037) from the control group. Although the means were not significantly different, 3 of 8 Ms and 5 of 8 SCZs also had rs values > the highest control value. Thermotropic behavior of the membranes was evaluated over the range of 40 to 20°C. No difference among groups in membrane enthalpy was detected. Thus, the differences in rs appear to be associated with differences in entropy. Phosphatidylcholine (PC) levels, which were known to be abnormal in these patients, were compared with the rs values. A significant (P < 0.001, R= -0.63) linear correlation between rs and membrane PC levels was observed. Overall these data further support the view that unusual membrane biophysical factors may occur with high frequency in the psychoses and affective disorders. 相似文献
The effects of size and hydrophobicity of small (molecular weights below 2,000) polypeptides on their predominantly hydrophobic interactions with a neutral phospholipid monolayer were studied. The changes in surface pressure were determined when various concentrations of Gly, Gly-Gly-Gly,
-Ala,
-Ala-
-Ala-
-Ala,
-Ala-Gly-Gly-Gly-Gly,
-Phe-
-Leu-
-Glu-
-Glu-
-Leu, adrenocorticotropic hormone fragments 1–10 (ACTH-(1–10)), porcine β-lipotropin, -endorphin and human fibrinopeptide A were injected under dimyristoylphosphatidylcholine (DMPC) monolayers at an initial surface pressure of 10 dyne/cm. In all cases, when peptides with the same number of residues are compared, the concentration needed to increase the surface pressure of the film by 1 dyne/cm was inversely related to its hydrophobicity. A reasonably good correlation was found to exist between the calculated free energy of transfer of a polypeptide from ethanol to water (a measure of its hydrophobicity) and its ability to increase the surface pressure of the DMPC film (a measure of the extent of its interaction with the neutral lipid monolayer). 相似文献
The determination of penetration pathways of topically applied substances into the skin is the subject of several investigations. Recently, follicular penetration has become a major focus of interest. To date, a direct, non-invasive quantification of the amount of topically applied substance penetrated into the follicles had not been possible. The development of such a method was the aim of this study. Therefore, the advantages of both stripping techniques, tape stripping and cyanoacrylate skin surface biopsy, were combined and evaluated. Tape stripping was used to remove the part of the stratum corneum that contained the topically applied dye. Subsequently, the follicular contents were ripped off by cyanoacrylate skin surface biopsy. The combined method termed "differential stripping" was evaluated in vitro and in vivo , and the amount of topically applied fluorescent dye penetrated into the hair follicles was quantified after different penetration times. After 30 min, 5% of the recovered concentration of sodium fluorescein was found in the follicular infundibula, where it was still detectable after 48 h. Altogether, the results of this investigation revealed that differential stripping is a new method that can be used to study the penetration of topically applied substances into the follicular infundibula non-invasively and selectively. 相似文献
It has earlier been proposed by the author that the aetiology of schizophrenic symptomatology may be due to the presence of abnormally connected interhemispheric fibres which link specialised functions in the brains of schizophrenics that are not connected in normal subjects, and that the neuroleptic drugs may produce their action through a local anaesthetic-like effect in suppression of conduction in these fibres. This line of thought has been extended here to consider the possible mechanism of action of the neuroleptic drugs in more detail, as well as that of the tricyclic antidepressant drugs which are derivatives of the phenothiazine group. Pharmacological similarities with the local anaesthetics both structurally and functionally have been considered, as well as the effects that these drug groups may have in common with the lithium salts. It has been suggested that these drugs all produce their primary effect on cell membranes, though not necessarily at the synapse, that the time course of their clinical effect may correlate with their incorporation into various cell membranes within the CNS, and that they may thus bring about a fundamental alteration in cell membrane microstructure. The possible role of electroconvulsive therapy has also been considered. The corollary of this argument is that the affective disorders may be genetically determined diseases of cell membrane microstructure. 相似文献