インスリン分泌性の、インシュリン分泌性の

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 健常者および疾患を有する患者における消化管ホルモンの概要 overview of gastrointestinal peptides in health and disease
2. 2型糖尿病のGlucagon-like peptide-1をベースとした治療 glucagon like peptide 1 based therapies for the treatment of type 2 diabetes mellitus
3. 上皮性卵巣癌、卵管癌、または原発性腹膜癌における血管新生阻害剤の作用 the role of angiogenesis inhibitors in epithelial ovarian fallopian tube or primary peritoneal cancer
4. 糖尿病の治療のためのアミリン類似体 amylin analogs for the treatment of diabetes mellitus
5. 肥満の病因 pathogenesis of obesity

English Journal

Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties.

Mabilleau G1, Mieczkowska A2, Irwin N3, Simon Y4, Audran M4, Flatt PR3, Chappard D5.Author information 1LUNAM Université, GEROM-LHEA, Institut de Biologie en Santé, Angers, France; LUNAM Université, SCIAM, Institut de Biologie en Santé, Angers, France. Electronic address: guillaume.mabilleau@univ-angers.fr.2LUNAM Université, GEROM-LHEA, Institut de Biologie en Santé, Angers, France.3School of Biomedical Sciences, University of Ulster, Coleraine, U K.4LUNAM Université, GEROM-LHEA, Institut de Biologie en Santé, Angers, France; Service de Rhumatologie, CHU d'Angers, Angers, France.5LUNAM Université, GEROM-LHEA, Institut de Biologie en Santé, Angers, France; LUNAM Université, SCIAM, Institut de Biologie en Santé, Angers, France.AbstractBone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone.
Bone.Bone.2014 Jun;63:61-8. doi: 10.1016/j.bone.2014.02.013. Epub 2014 Mar 1.
Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzym
PMID 24594344

Dipeptidyl Peptidase IV Inhibitors: A New Paradigm in Type 2 Diabetes Treatment.

Janardhan S, Sastry GN1.Author information 1Centre for Molecular Modeling, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad- 500 607, India. sridharajanardhan@gmail.com.AbstractDipeptidyl peptidase IV (DPP4) is a promising target for the treatment of chronic metabolic type 2 diabetes mellitus (T2D). DPP4 is a highly specific serine protease involved in the regulation and cleavage of two incretin hormones, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These incretin hormones are released by the gastrointestinal tract in response to ingestion of food and stimulate insulin secretion and thereby regulate glucose homeostasis with a low risk of hypoglycemia and glucagon secretion. Currently different chemical classes of DPP4 inhibitors are in last-stage of clinical trials and few of them such as sitagliptin, vildagliptin, saxagliptin alogliptin and linagliptin have already been successfully released into market. These drugs have been approved as either monotherapy or combination therapy with other oral hypoglycemic agents such as metformin, pioglitazone, sulfonylurea, glyburide and glibenclamide for the treatment of T2D. Though several clinical trial compounds were discontinued because of severe adverse toxic effects that are associated with other prolyldipeptidases include DPP8 and DPP9. The current review provides an overview of DPP4 and its inhibitors with emphasis on the structure, expression, activity, selectivity and pharmacokinetics information. This review further dwells upon the issues relating to the rational design and development of selective DPP4 inhibitors for the treatment of T2D.
Current drug targets.Curr Drug Targets.2014 Jun;15(6):600-21.
Dipeptidyl peptidase IV (DPP4) is a promising target for the treatment of chronic metabolic type 2 diabetes mellitus (T2D). DPP4 is a highly specific serine protease involved in the regulation and cleavage of two incretin hormones, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic p
PMID 24611684

Effects of consumption of main and side dishes with white rice on postprandial glucose, insulin, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 responses in healthy Japanese men.

Kameyama N1, Maruyama C1, Matsui S2, Araki R2, Yamada Y3, Maruyama T4.Author information 1Division of Food and Nutrition, Graduate School of Human Sciences and Design, Japan Women's University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681, Japan.2Department of Food and Nutrition, Faculty of Human Sciences and Design, Japan Women's University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681, Japan.3Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City, Akita 010-8543, Japan.4Department of Internal Medicine, Saitama Social Insurance Hospital, 4-9-3 Kitaurawa, Urawa-ku, Saitama City, Saitama 330-0074, Japan.AbstractThe co-ingestion of protein, fat and fibre with carbohydrate reportedly affects postprandial glucose, insulin and incretin (glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)) responses. However, the effects of combination dishes with carbohydrate-rich foods at typically eaten amounts remain unclear. The objective of the present study was to evaluate the effects of consuming recommended amounts of side dishes with boiled white rice in the same meal on postprandial plasma glucose, insulin and incretin hormone responses. A total of nine healthy male volunteers consumed four different meals in a random order on separate days. The test meals were as follows: S, white rice; SM, addition of protein-rich main dishes to the S meal; SMF, addition of a fat-rich food item to the SM meal; SMFV, addition of vegetables to the SMF meal. Plasma glucose, GIP and GLP-1 and serum insulin concentrations were determined during a 3 h period after consumption of these meals. Postprandial glucose responses were lower after SMFV meal consumption than after consumption of the other meals. The incremental AUC for GIP (0-180 min) were largest after consumption of the SMF and SMFV meals, followed by that after SM meal consumption, and was smallest after S meal consumption (P< 0·05). Furthermore, we found GIP concentrations to be dose dependently increased by the fat content of meals of ordinary size, despite the amount of additional fat being small. In conclusion, the combination of recommended amounts of main and vegetable side dishes with boiled white rice is beneficial for lowering postprandial glucose concentrations, with an increased incretin response, when compared with white rice alone.
The British journal of nutrition.Br J Nutr.2014 May;111(9):1632-40. doi: 10.1017/S0007114513004194. Epub 2014 Feb 10.
The co-ingestion of protein, fat and fibre with carbohydrate reportedly affects postprandial glucose, insulin and incretin (glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)) responses. However, the effects of combination dishes with carbohydrate-rich foods at ty
PMID 24507870