We have compared the capillary density and muscle fiber type of musculus vastus lateralis with in vivo insulin action determined by the euglycemic clamp (M value) in 23 Caucasians and 41 Pima Indian nondiabetic men. M value was significantly correlated with capillary density (r = 0.63; P < 0.0001), percent type I fibers (r = 0.29; P < 0.02), and percent type 2B fibers (r = -0.38; P < 0.003). Fasting plasma glucose and insulin concentrations were significantly negatively correlated with capillary density (r = -0.46, P . 0.0001; r = -0.47, P . 0.0001, respectively). Waist circumference/thigh circumference ratio was correlated with percent type 1 fibers (r = -039; P < 0.002). These results suggest that diffusion distance from capillary to muscle cells or some associated biochemical change, and fiber type, could play a role in determining in vivo insulin action. The association of muscle fiber type with body fat distribution may indicate that central obesity is only one aspect of a more generalized metabolic syndrome. The data may provide at least a partial explanation for the insulin resistance associated with obesity and for the altered kinetics of insulin action in the obese.

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Xanthophylls have a crucial role in the structure and function of the light harvesting complexes of photosystem II (LHCII) in plants. The binding of xanthophylls to LHCII has been investigated, particularly with respect to the xanthophyll cycle carotenoids violaxanthin and zeaxanthin. It was found that most of the violaxanthin pool was loosely bound to the major complex and could be removed by mild detergent treatment. Gentle solubilization of photosystem II particles and thylakoids allowed the isolation of complexes, including a newly described oligomeric preparation, enriched in trimers, that retained all of the in vivo violaxanthin pool. It was estimated that each LHCII monomer can bind at least one violaxanthin. The extent to which different pigments can be removed from LHCII indicated that the relative strength of binding was chlorophyll b > neoxanthin > chlorophyll a > lutein > zeaxanthin > violaxanthin. The xanthophyll binding sites are of two types: internal sites binding lutein and peripheral sites binding neoxanthin and violaxanthin. In CP29, a minor LHCII, both a lutein site and the neoxanthin site can be occupied by violaxanthin. Upon activation of the violaxanthin de-epoxidase, the highest de-epoxidation state was found for the main LHCII component and the lowest for CP29, suggesting that only violaxanthin loosely bound to LHCII is available for de-epoxidation.Xanthophylls are a class of carotenoids associated with the light harvesting complexes of plant chloroplast membranes (1). In most plants, there are three major xanthophylls, namely lutein, neoxanthin, and violaxanthin, the last of which can be reversibly de-epoxidized to antheraxanthin and zeaxanthin via the xanthophyll cycle (2). The reason for this diversity in xanthophyll composition is not entirely clear, although the conservation of xanthophyll composition across a range of plant species (3-5) indicates a specific role for each one. Although xanthophylls are bound to both LHCII 1 and LHCI, the nature of the binding has not been determined, and there are significant differences in the values reported for the numbers of pigments bound to particular complexes (6 -11). In the structural model for the major LHCII component, LHCIIb, there are two carotenoid molecules that are presumed to be the two luteins that have been shown to be bound by this complex (12). No other carotenoids were detected in this crystallographic study, despite the fact that there are either one or two other carotenoids present. For the other LHCII components, CP29, CP26, and CP24, there is even less certainty, with estimates of the number of bound carotenoids differing significantly (see reviews in Refs. 9 and 11).In the case of the xanthophyll cycle carotenoids, establishing the stoichiometry of binding is of particular importance because this cycle plays a major role in controlling the efficiency of light harvesting (5, 13, 14): in light-limiting conditions, maximum efficiency of light harvesting is associated with the presence of violaxanthin, whereas de-epoxidation ...

Exendin-4 is a 39 amino acid peptide isolated from the salivary secretions of the Gila monster (Heloderma suspectum). It shows 53% sequence similarity to glucagon-like peptide (GLP)-1. Unlike GLP-1, exendin-4 has a prolonged glucose-lowering action in vivo. We compared the potency and duration of glucose-lowering effects of exendin-4 and GLP-1 in hyperglycemic db/db and ob/ob mice. Whereas reductions in plasma glucose of up to 35% vanished within 1 h with most doses of GLP-1, the same doses of exendin-4 resulted in a similar glucose-lowering effect that persisted for >4 h. Exendin-4 was 5,530-fold more potent than GLP-1 in db/db mice (effective doses, 50% [ED50s] of 0.059 microg/kg +/-0.15 log and 329 microg/kg+/-0.22 log, respectively) and was 5,480-fold more potent in ob/ob mice (ED50s of 0.136 microg/kg+/-0.10 log and 744 microg/kg+/-0.21 log, respectively) when the percentage fall in plasma glucose at 1 h was used as the indicator response. Exendin-4 dose-dependently accelerated glucose lowering in diabetic rhesus monkeys by up to 37% with an ED50 of 0.25 microg/kg +/-0.09 log. In two experiments in which diabetic fatty Zucker rats were injected subcutaneously twice daily for 5-6 weeks with doses of exendin-4 up to 100 microg x rat(-1) x day(-1) (approximately 250 microg/kg), HbA1c was reduced relative to saline-injected control rats. Exendin-4 treatment was also associated in each of these experiments with weight loss and improved insulin sensitivity, as demonstrated by increases of up to 32 and 49%, respectively, in the glucose infusion rate (GIR) in the hyperinsulinemic euglycemic clamp. ED50s for weight loss and the increase in clamp GIR were 1.0 microg/kg+/-0.15 log and 2.4 microg/kg+/-0.41 log, respectively. In conclusion, acute and chronic administration of exendin-4 has demonstrated an antidiabetic effect in several animal models of type 2 diabetes.

Green plants use the xanthophyll cycle to regulate the flow of energy to chlorophylla within photosynthetic proteins. Under conditions of low light intensity violaxanthin, a carotenoid possessing nine conjugated double bonds, functions as an antenna pigment by transferring energy from its lowest excited singlet state to that of chlorophylla within light-harvesting proteins. When the light intensity increases, violaxanthin is biochemically transformed into zeaxanthin, a carotenoid that possesses eleven conjugated double bonds. The results presented here show that extension of the [Symbol: see text] conjugation of the polyene lowers the energy of the lowest excited singlet state of the carotenoid below that of chlorophylla. As a consequence zeaxanthin can act as a trap for the excess excitation energy on chlorophylla pigments within the protein, thus regulating the flow of energy within photosynthetic light-harvesting proteins.

~~l h e xanthophyll composition of the light-harvesting chlorophyll a/b proteins of photosystem II (LHCII) has been determined for spinach (Spinacia oleracea 1.) leaves after dark adaptation and following illumination under conditions optimized for conversion of violaxanthin into zeaxanthin. Each of the four LHCll components was found to have a unique xanthophyll composition. l h e major carotenoid was lutein, comprising 60% of carotenoid in the bulk LHCllb and 35 to 50% in the minor LHCll components LHClla, LHCllc, and LHClld. l h e percent of carotenoid found in the xanthophyll cycle pigments was approximately 10 to 15% in LHCllb and 30 to 40% in LHClla, LHCllc, and LHCIU. l h e xanthophyll cycle was active for the pigments bound to all of the LHCll components. The extent of deepoxidation for complexes prepared from light-treated leaves was 27, 65, 69, and 43% for LHClla, -b, -c, and -d, respectively. lhese levels of conversion of violaxanthin to zeaxanthin were found in LHCll prepared by three different isolation procedures. It was estimated that approximately 50% of the zeaxanthin associated with photosystem II is in LHCllb and 30% is associated with the minor LHCll components.Leaves exposed to irradiance levels that are in excess of those capable of being utilized with maximum quantum yield induce nonphotochemical thermal dissipation of the excessabsorbed photons. Thermal dissipation is a mechanism for short-term adaptation to changes in irradance, thereby protecting against photodamage to the photosynthetic membrane (Demmig-Adams and Adams, 1992a). This process is known as nonphotochemical quenching of Chl fluorescence, since increased heat evolution reduces fluorescence yield (Horton and Bowyer, 1990;Krause and Weis, 1991). There are three important features of nonphotochemical quenching of Chl fluorescence. First, the major part of it is induced as a result of the acidification of the thylakoid lumen that is associated with the formation of the proton motive force and has been referred to as qE (Briantais et al., 1979). Second, qE is a process by which energy is dissipated in the lightharvesting system of PSII, most probably in the LHCII protein complexes (Horton et al