title: Early liraglutide treatment is better in glucose control, β-cell function improvement and mass preservation in db/db mice.
abstract: Glucagon-like peptide-1 (GLP-1) has been proved to have effects of anti-hyperglycemia and β-cell preservation. However, it is still unclear whether there are differences between early and late GLP-1 intervention in type 2 diabetes mellitus (T2DM). We divided the mice into 5 groups: early treated group (n=7, 8-week old, fasting glucose>10mmol/l), late treated group (n=7, 10-week old, fasting glucose>20mmol/l), early control group (n=7), late control group (n=7) and wild type group (n=7). Treated group was injected with liraglutide (a GLP-1 analog) 300μg/kg bid for 4 weeks, while control group was given saline at the same time. The results showed that compared with control group, food intake and body weight gain were reduced in both early and late treated group (p<0.05), and there was no significance between the two treated groups. Early liraglutide intervention showed better improvements in glucose control, acute insulin response to glucose (AIRg) and disposition index (before vs. after treatment, AIRg 1.01±0.53 vs. 2.98±0.63, disposition index 10.81±0.89 vs. 27.4±2.15) than late intervention (AIRg 0.99±0.02 vs. 1.41±0.32, disposition index 3.47±0.38 vs. 6.43±1.62, p=0.001). The histopathology of the pancreas showed the estimated β-cell mass (BCM) was increased more in early treated group than that in late one (0.03 vs. 0.01g). Expressions of the proliferation related genes PDX-1, MafA and GLP-1 receptor (GLP-1R) in early treated group were 1.81, 2.57 and 1.59 times as much as that in late treated group. In conclusion, early liraglutide intervention was better in glucose control, β-cell function improvement and β-cell mass preservation.
authors.affiliation: Endocrinology Department, Peking University First Hospital, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Endocrinology Department, Peking University First Hospital, China. Electronic address: 139197109@qq.com.
authors.forename: Geheng
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Huguosi Hospital of Traditional Chinese Medicine, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Endocrinology Department, Peking University First Hospital, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Endocrinology Department, Peking University First Hospital, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004435:Eating / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D000069450:Liraglutide; D051473:Maf Transcription Factors, Large / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018027:Receptors, Glucagon / Q000096:biosynthesis; D015534:Trans-Activators / Q000096:biosynthesis
chemical_list: C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D018027:Receptors, Glucagon; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005947:Glucose
keywords: Early intervention; Liraglutide; T2DM; β-Cell