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Metformin causes reduction of food intake and body weight gain and improvement of glucose intolerance in combination with dipeptidyl peptidase IV inhibitor in Zucker fa/fa rats.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Yasuda, Nobuyuki Inoue, Takashi Nagakura, Tadashi Yamazaki, Kazuto Kira, Kazunobu Saeki, Takao Tanaka, Ittetsu |
| Copyright Year | 2004 |
| Abstract | An incretin hormone, glucagon-like peptide-1 (GLP-1), has been shown to lower plasma glucose via glucose-dependent insulin secretion and to reduce appetite. We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats. This finding suggested that the combination treatment might produce a greater antidiabetic and anorectic effect, based on enhanced GLP-1 action. In this study, we assessed the effects of subchronic treatment with metformin and a DPPIV inhibitor, valine-pyrrolidide (val-pyr), on glycemic control, food intake, and weight gain using Zucker fa/fa rats, a model of obesity and impaired glucose tolerance. The combination treatment caused a significant increase of GLP-1 level in Zucker fa/fa rats. In a subchronic study, val-pyr, metformin, or both compounds were administered orally b.i.d. for 14 days. The combination treatment significantly decreased food intake and body weight gain, although neither metformin nor val-pyr treatment alone had any effect. In an oral glucose tolerance test on day 1, the coadministration caused a greater improvement of glucose tolerance and a prominent increase of plasma active GLP-1 without marked insulin secretion. The 14-day combination treatment produced a potent reduction of fasting blood glucose and plasma insulin levels. These results demonstrate that the combination therapy of metformin with DPPIV inhibitor leads to reduced food intake and body weight gain, most likely through the significant increase of plasma GLP-1 level. The combination therapy seems to be a good candidate for treatment of type 2 diabetes with obesity. |
| Starting Page | 1 |
| Ending Page | 7 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jpet.aspetjournals.org/content/jpet/310/2/614.full.pdf |
| PubMed reference number | 15039452v1 |
| Volume Number | 310 |
| Issue Number | 2 |
| Journal | The Journal of pharmacology and experimental therapeutics |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Anorexia Antidiabetics Biguanides Body Dysmorphic Disorders Body Weight Gain Domain Combined Modality Therapy Desire for food Diabetes Mellitus Diabetes Mellitus, Non-Insulin-Dependent Dipeptidyl-Peptidase IV Eating Folic Acid Glucagon Glucagon-Like Peptide 1 Glucagon-Like Peptide-1 Receptor Glucose tolerance test Hematological Disease Heparin, Low-Molecular-Weight Impaired glucose tolerance Incretins Metformin Obesity Oral cavity Peptide Hydrolases Peptidyl-Dipeptidase A Proteolytic Enzyme Valine Valine/Creatinine:MRto:24H:Urine:Qn Z, Rat Strain insulin secretion |
| Content Type | Text |
| Resource Type | Article |
