KTO-7924, a Beta3-adrenergic receptor agonist, reduces hyperglycemia, and protects beta-cells in the islets of langerhans of db/db mice.
BACKGROUND
The effect of beta3-adrenergic receptor agonists on beta cells in the islets of Langerhans is not yet clear. This study examined the beta3-adrenergic receptor agonist on beta cells in the islets of Langerhans.


METHODS
Obese diabetic C57BL/KsJ-db/db mice were treated with KTO-7924, a newly-developed beta3-adrenergic receptor agonist for 28-day. We analyzed plasma parameters, insulin resistance, and insulin-positive areas among beta-cells in the islets of Langerhans.


CONCLUSIONS
After a 28-day oral administration period, plasma levels of hemoglobin (Hb) A1c, glucose, triglyceride (TG), and free fatty acid (FFA) were all significantly reduced in KTO-7924 treatment groups compared with controls. Plasma adiponectin levels decreased with age in the control group, but were significantly higher in a treatment group throughout the study period. Furthermore, sequential administration of KTO-7924 led to an improvement in insulin resistance in the OGTT (Oral glucose tolerance test (OGTT)), and an increase in the percentage of insulin-positive areas among beta-cells in the islets of Langerhans compared with controls. This is the first study to show islet histology after treatment of a beta3-adrenergic receptor agonist, and reveals that KTO-7924 reduces hyperglycemia, and protects beta-cells in the islets of Langerhans of db/db mice.
Oana
Fumiki
F
Division of Discovery Research, Kissei Pharmaceutical Company Ltd., Hotaka, Nagano, Japan. fumiki_oana@pharm.kissei.co.jp
Takeda
Hiroo
H
Matsuzawa
Akane
A
Akahane
Satoshi
S
Hayashi
Morimichi
M
Tamura
Toru
T
Uehara
Miyuki
M
Isaji
Masayuki
M
Akahane
Masuo
M
D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D000322:Adrenergic Agonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007328:Insulin; D012313:RNA; D014280:Triglycerides