Characterization of CS-045, a new oral antidiabetic agent, II. Effects on glycemic control and pancreatic islet structure at a late stage of the diabetic syndrome in C57BL/KsJ-db/db mice

Metabolism. 1991 Nov;40(11):1213-8. doi: 10.1016/0026-0495(91)90218-l.


Antidiabetic effects of CS-045 were evaluated in 5-month-old C57BL/KsJ-db/db mice (db/db). CS-045 administered for 3 weeks to diabetic db/db mice as a 0.2% food admixture improved hyperglycemia (855 +/- 25 v 298 +/- 62 mg/dL, P less than .01) and glucose intolerance, and lowered plasma triglyceride (299.6 +/- 28.7 v 76.3 +/- 20.7 mg/dL, P less than .01) and free fatty acid (FFA) levels (1.16 +/- 0.14 v 0.57 +/- 0.07 mEq/L, P less than .01). Food intake was not changed, while a small but significant increase in body weight was observed in CS-045-treated mice. Plasma insulin levels gradually increased after 5 days of CS-045 treatment, and a nonsignificant increase was observed in plasma insulin levels after 3 weeks (1.85 +/- 0.50 v 4.54 +/- 1.47 mg/mL). In contrast, the plasma glucagon levels decreased after 3 weeks of CS-045 treatment. Histological examination by aldehyde-fucshin staining demonstrated that pancreatic beta cells in CS-045-treated db/db mice were heavily regranulated, whereas most of the beta cells were extensively degranulated in nontreated db/db mice. The heavily regranulated state of beta cells was also compatible with an increase in pancreatic insulin content in CS-045-treated db/db mice. Electron microscopic analysis showed a well-developed endoplasmic reticulum and the accumulation of much amorphous structural material in the intracisternal space of beta cells from CS-045-treated db/db mice, which were suggestive of an increase in insulin synthesis. Moreover, CS-045 treatment decreased exocrine-containing islets, which was associated with the islets' degeneration process. Immunohistochemical staining of islets showed that CS-045 treatment normalized the distribution pattern of endocrine cells in the islets of db/db mice, reflected by a predominantly peripheral location of alpha and delta cells.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / analysis*
  • Chromans / pharmacology*
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / pathology
  • Glucagon / analysis
  • Hyperglycemia / blood*
  • Hyperglycemia / genetics
  • Hyperglycemia / pathology
  • Hyperinsulinism / blood*
  • Hyperinsulinism / genetics
  • Hyperinsulinism / pathology
  • Hypoglycemic Agents / pharmacology
  • Insulin / analysis
  • Islets of Langerhans / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pancreas / chemistry
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Troglitazone


  • Blood Glucose
  • Chromans
  • Hypoglycemic Agents
  • Insulin
  • Thiazoles
  • Thiazolidinediones
  • Glucagon
  • Troglitazone