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.

1.° Appiani Lybicorum vetus interpretatio : initium et finis desiderantur. — 2.° Homeri batrachomyomachia, à Carolo Aretino versibus hexametris reddita. — 3.° Carmina de praecipuis Italiae urbibus. — 4.° Carmen cui titulus : Ovidius de Lombardo et Lumaca. — 5.° Adjectivationes Leonardi Aretini : sunt autem eae adjectivationes, varii modi quibus litterae debent inscribi.

Tellerianus

Modi di dire

Encyclopedia entry for "idioms" and "idiomatic expressions" in Italian

Audiovisivi e Social Networks: il testo e i modi dell'esperienza 2007-2010

The doctoral research project "Audiovisuals and Social Networks: Text and Experiences 2007-2010" is mainly based on the analysis of the international audiovisuals landscape and of the promotional strategies of these products in Social Networks environment. The aim is to understand what kind of changes we can find about the concept of "text", users and marketing. The thesis is focused not just on Social Network marketing but also on new media development, such as Social TV and mobile.

Modi's Reform Agenda: Change You Can Believe In? Asia Policy Brief 2015/04, November 2015

Indian Prime Minister Narendra Modi entered office with a historic political mandate. For the first time in thirty years, a single party won a majority of seats in the lower house of Parliament (Lok Sabha). However, Modi faces skyhigh expectations to fulfill his campaign promises of getting India’s economy back on track. Eighteen months into his government’s term and in the wake of electoral defeats in the states of Delhi and Bihar, questions are being raised about its economic performance. While the Modi government has stabilized India’s macroeconomy and announced a series of incremental economic reforms, more sweeping changes have fallen victim to India’s nettlesome domestic politics, including roadblocks within the ruling alliance.

Raccolta di pensieri e modi errati (1867) /

"Opere edite a cura della Signora Bianca Bovio."--Back cover.

Della architettvra militare del capitanio Francesco de' Marchi bolognese, gentil'hvomo romano, libri tre : nelli qvali si descrivono li veri modi del fortificare, che si vsa a' tempi moderni : con vn breve, et vtile trattato, nel quale si dimostrano li modi del fabricar l'artigliaria, & la prattica di adoperarla, da quelli che hanno carico di essa.

[superscript pi]A² a2-a4 b² A-F⁶ G⁸ H-2O² [2P]⁸ 2Q² 2R⁴ 2S² 2T-2X⁶ 2Y⁴ 2Z-3A² 3B⁸ 3C-6T² [6V-6Z]² [dagger-2 daggers]⁶ chi-2chi².