Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

BackgroundA soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.MethodsWe assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).ResultsFasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.ConclusionSerum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.     

Intracellular regulation of cell signaling cascades: how location makes a difference

Organelles such as endosomes and the Golgi apparatus play a critical role in regulating signal transmission to the nucleus. Recent experiments have shown that appropriate positioning of these organelles within the intracellular space is critical for effective signal regulation. To understand the mechanism behind this observation, we consider a reaction-diffusion model of an intracellular signaling cascade and investigate the effect on the signaling of intracellular regulation in the form of a small release of phosphorylated signaling protein, kinase, and/or phosphatase. Variational analysis is applied to characterize the most effective regions for the localization of this intracellular regulation. The results demonstrate that signals reaching the nucleus are most effectively regulated by localizing the release of phosphorylated substrate protein and kinase near the nucleus. Phosphatase release, on the other hand, is nearly equally effective throughout the intracellular space. The effectiveness of the intracellular regulation is affected strongly by the characteristics of signal propagation through the cascade. For signals that are amplified as they propagate through the cascade, reactions in the upstream levels of the cascade exhibit much larger sensitivities to regulation by release of phosphorylated substrate protein and kinase than downstream reactions. On the other hand, for signals that decay through the cascade, downstream reactions exhibit larger sensitivity than upstream reactions. For regulation by phosphatase release, all reactions within the cascade show large sensitivity for amplified signals but lose this sensitivity for decaying signals. We use the analysis to develop a simple model of endosome-mediated regulation of cell signaling. The results demonstrate that signal regulation by the modeled endosome is most effective when the endosome is positioned in the vicinity of the nucleus. The present findings may explain at least in part why endosomes in many cell types localize near the nucleus.     

The receptor of calcitonin gene-related peptide (CGRP) is present on the membranes of insulinoma

We demonstrate here that membranes prepared from beta cells which release insulin contain specific binding sites for calcitonin gene-related peptide (CGRP). The binding of 125I(His) human CGRP to beta cell membranes was protein concentration, time, temperature and pH dependent. Scatchard analysis of the data revealed a single class of binding sites with an apparent dissociation constant (Kd) of 1.5 nM and a maximal binding capacity of 19 fmol/mg of protein. Chicken CGRP inhibited the label binding whereas salmon calcitonin had only a weak effect. These results suggest that the effect of CGRP on insulin secretion is due to a direct action on beta cells.     

Enriching marine macroalgae with eicosatetraenoic (arachidonic) and eicosapentaenoic acids by chilling

Summary Twelve macroalgae belonging to the Chlorophyta, Phaeophyta and Rhodophyta were collected from the Arabian Gulf. Field samples and samples that were first incubated at 5° C and 24° C in the light for 1 week were analysed for lipids and fatty acids. The lipid contents varied according to the macroalga and, within the Chlorophyta and Phaeophyta, some representatives accumulated more lipids at 5° C and others at 24° C. All samples of algae had similar lipid composition with only quantitative differences. The temperature did not have a common effect on the lipid composition of representative algae, although changes in the relative concentration of specific classes were recorded. The Phaeophyta and Rhodophyta were as a rule richer than the Chlorophyta in eicosatetranoic (20:4) and eicosapentaenoic (20:5) but poorer in linolenic (18:3) acids. In most of the algae, incubation at 5° C was associated with lowering the proportion of palmitic acid (16:0) in the total lipids, and, but only in the Phaeophyta and Rhodophyta, increasing the concentration of 20:4 and 20:5. These polyunsaturated fatty acids occurred in high levels in monogalactosyldiacylglycerols (MGDG) and digalactosyldiacylglycerols (DGDG) of the Phaeophyta and Rhodophyta but not the Chlorophyta, the MGDG and DGDG of which were rich in 18:3 and hexadecatrienoic acid (16:3). Offprint requests to: R. H. Al-Hasan     

Protein metabolism during endurance exercise

After reviewing all the available results from our laboratory and numerous reports in the literature concerning changes that have occurred in various aspects of protein metabolism during exercise, a number of conclusions can be drawn with some degree of confidence. During exercise, protein synthesis is depressed and this change leaves amino acids available for catabolic processes. The rate of leucine oxidation appears to be increased during exercise, and there is a movement of amino acids, mostly in the form of alanine, from muscle to liver where the rate of gluconeogenesis is increased as a result of exercise. These changes in protein metabolism are probably physiologically significant in at least three ways: amino acid conversion to citric acid cycle intermediates enhances the rate of oxidation of acetyl-CoA generated from glucose and fatty acid oxidation; increased conversion of amino acids to glucose helps to prevent hypoglycemia; oxidation of some amino acids may provide energy for muscular contraction.     

An assessment of the cultural capabilities of protoplasts of some wild species of linum

Protoplasts of several wildLinum species were isolated enzymatically from roots, hypocotyls and cotyledons of seedlings, and also from theirin vitro grown shoots and cell suspension cultures. When cultured all these protoplasts divided to produce callus but only good plant regeneration capability was evident in the case ofLinum lewissii and to a much lesser extent forL. strictum. Only rhizogenesis was observed withL. alpinum, L. narbonense, L. grandiflorum andL. altaicum. The high plant regeneration capacity ofL. lewissii from protoplast -derived tissues ofin vitro shoots and cell suspension cultures makes this species an attractive experimental system for somatic genetic manipulation.Abbreviations BAP benzylaminopurine - NAA -naphthaleneacetic acid - CPW cell and protoplast wash solution - gFW gram fresh weight On leave from Department of Crop Sciences University of Alexandria Egypt     

Uptake and utilization of n-octacosane and n-nonacosane by Arthrobacter nicotianae KCC B35

Arthrobacter nicotianae KCC B35 isolated from blue-green mats densely covering oil sediments along the Arabian Gulf coast grew well on C₁₀ to C₄₀ n -alkanes as sole sources of carbon and energy. Growth on C₂₀ to C₄₀ alkanes was even better than on C₁₀ to C₁₈ alkanes. Biomass samples incubated for 6 h with n -octacosane (C₂₈) or n -nonacosane (C₂₉) accumulated these compounds as the predominant constituent alkanes of the cell hydrocarbon fractions. The even chain hexadecane C₁₆ and the odd chain pentadecane C₁₅ were the second dominant constituent alkanes in C₂₈ and C₂₉ incubated cells, respectively. n -Hexadecane-incubated cells accumulated in their lipids higher proportions of C₁₆-fatty acids than control cells not incubated with hydrocarbons. On the other hand, C₂₈ and C₂₉-incubated cells did not contain any fatty acids with the equivalent chain lengths, but the fatty acid patterns of the cell lipids suggest that there should have been mid-chain oxidation of these very long chain alkanes. This activity qualifies A. nicotianae KCC B35 to be used in cocktails for bioremediating environments polluted with heavy oil sediments.     

Soil management enhancing hydrocarbon biodegradation in the polluted Kuwaiti desert

Oil-polluted Kuwaiti desert samples, exposed to the open air, were subjected to specific types of management, once every 2 weeks, throughout a year; control samples were not treated. The total amounts of extractable alkanes from the control samples remained fairly constant during the dry hot months, but decreased during the rainy months reaching, after 1 year, slightly more than one-half of the amount at zero time. This result demonstrates the self-cleaning of the Kuwaiti desert and the essential role of moisture in this process. Out of the eight types of management studied, the repeated fertilization of the polluted sample with 3% KNO₃ solution was most efficient, reducing the extractable alkanes after 1 year to about one-third of zero reading. Repeated fertilization with treated sewage effluent was inhibitory to alkane biodegradation, probably because of increasing soil acidity. The latter inhibitory effect was annulled by liming. Repeated irrigation with 3% NaCl solution was inhibitory, but 1% NaCl solution slightly promoted alkane biodegradation. The various samples contained 10¹⁰–10¹¹ oil-utilizing bacteria/g soil, predominantly Bacillus, Pseudomonas, Rhodococcus and Streptomyces. Oil-utilizing fungi were much less frequent and were predominantly Aspergillus and Penicillium species. The microbial numbers varied not only according to the type of soil management but also to the season.