Evaluation of the antidiabetic activity of DPP IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependent insulinotropic polypeptide

Glucose dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with therapeutic potential for type 2 diabetes due to its insulin-releasing and antihyperglycaemic actions. However, development of GIP-based therapies is limited by N-terminal degradation by DPP IV resulting in a very short circulating half-life. Numerous GIP analogues have now been generated exhibiting DPP IV resistance and extended bioactivity profiles. In this study, we report a direct comparison of the long-term antidiabetic actions of three such GIP molecules, N-AcGIP, GIP(LyS(37)PAL) and N-AcGIP(LyS(37)PAL) in obese diabetic (ob/ob) mice. An extended duration of action of each GIP analogue was demonstrated prior to examining the effects of once daily injections (25 nmol kg(-1) body weight) over a 14-day period. Administration of either N-AcGIP, GIP(LyS(37)PAL) or N-AcGIP(LyS37PAL) significantly decreased non-fasting plasma glucose and improved glucose tolerance compared to saline treated controls. All three analogues significantly enhanced glucose and nutrient-induced insulin release, and improved insulin sensitivity. The metabolic and insulin secretory responses to native GIP were also enhanced in 14-day analogue treated mice, revealing no evidence of GIP-receptor desensitization. These effects were accompanied by significantly enhanced pancreatic insulin following N-AcGIP(Lys(37)PAL) and increased islet number and islet size in all three groups. Body weight, food intake and circulating glucagon were unchanged. These data demonstrate the therapeutic potential of once daily injection of enzyme resistant GIP analogues and indicate that N-AcGIP is equally as effective as related palmitate derivatised analogues of GIP. (c) 2006 Elsevier Inc. All rights reserved.

Gayliella gen. nov in the tribe Ceramieae (Ceramiaceae, Rhodophyta) based on molecular and morphological evidence

On the basis of comparative morphology and phylogenetic analyses of rbcL and LSU rDNA sequence data, a new genus, Gayliella gen. nov., is proposed to accommodate the Ceramium flaccidum complex (C. flaccidum, C. byssoideum, C. gracillimum var. byssoideum, and C. taylorii), C. fimbriatum, and a previously undescribed species from Australia. C. transversale is reinstated and recognized as a distinct species. Through this study, G. flaccida (Kutzing) comb. nov., G. transversalis (Collins et Hervey) comb. nov., G. fimbriata (Setchell et N. L. Gardner) comb. nov., G. taylorii comb. nov., G. mazoyerae sp. nov., and G. womersleyi sp. nov. are based on detailed comparative morphology. The species referred to as C. flaccidum and C. dawsonii from Brazil also belong to the new genus. Comparison of Gayliella with Ceramium shows that it differs from the latter by having an alternate branching pattern; three cortical initials per periaxial cell, of which the third is directed basipetally and divides horizontally; and unicellular rhizoids produced from periaxial cells. Our phylogenetic analyses of rbcL and LSU rDNA gene sequence data confirm that Gayliella gen. nov. represents a monophyletic clade distinct from most Ceramium species including the type species, C. virgatum. We also transfer C. recticorticum to the new genus Gayliella.