Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to beta-cells in streptozotocin-treated mice.
Betacellulin (BTC) induces differentiation of pancreatic beta-cells and promotes regeneration of beta-cells in experimental diabetes. The present study was conducted to determine if BTC improved glucose metabolism in severe diabetes induced by a high dose of streptozotocin (STZ) in mice. Male ICR mice were injected with 200 microg/g ip STZ, and various doses of BTC were administered daily for 14 days. The plasma glucose concentration increased to a level of >500 mg/dl in STZ-injected mice. BTC (0.2 microg/g) significantly reduced the plasma glucose concentration, but a higher concentration was ineffective. The effect of BTC was marked by day 4 but became smaller on day 6 or later. The plasma insulin concentration and the insulin content were significantly higher in mice treated with 0.1 and 0.2 microg/g BTC. BTC treatment significantly increased the number of beta-cells in each islet as well as the number of insulin-positive islets. Within islets, the numbers of 5-bromo-2-deoxyuridine/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells were significantly increased by BTC. These results indicate that BTC improved hyperglycemia induced by a high dose of STZ by promoting neoformation of beta-cells, mainly from somatostatin-positive islet cells.
Li
Lei
L
Institute for Molecular and Cellular Regulation, Gunma Univ., Maebashi 371-8512, Japan.
Seno
Masaharu
M
Yamada
Hidenori
H
Kojima
Itaru
I
D000818:Animals; D066259:Betacellulin; D001786:Blood Glucose / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
D066259:Betacellulin; D001786:Blood Glucose; C587852:Btc protein, mouse; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins