Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to β-cells in streptozotocin-treated mice

Lei Li, Masaharu Seno, Hidenori Yamada, Itaru Kojima

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53 Citations (Scopus)

Abstract

Beta-cellulin (BTC) induces differentiation of pancreatic β-cells and promotes regeneration of β-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 μg/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 μg/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 μg/g BTC. BTC treatment significantly increased the number of β-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 β-cells, mainly from somatostatin-positive islet cells.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number3 48-3
Publication statusPublished - Sep 1 2003

Fingerprint

Streptozocin
Metabolism
Somatostatin-Secreting Cells
Somatostatin
Glucose
Insulin
Medical problems
Plasmas
Cells
Inbred ICR Mouse
Homeobox Genes
Bromodeoxyuridine
Islets of Langerhans
Hyperglycemia
Regeneration
Cell Differentiation
Cell Count
Betacellulin

Keywords

  • Pancreas

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

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abstract = "Beta-cellulin (BTC) induces differentiation of pancreatic β-cells and promotes regeneration of β-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 μg/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 μg/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 μg/g BTC. BTC treatment significantly increased the number of β-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 β-cells, mainly from somatostatin-positive islet cells.",
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