Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combination therapy with epidermal growth factor (EGF) and gastrin induces beta-cell regeneration in rodents with chemically induced diabetes. We investigated whether EGF plus gastrin could correct hyperglycemia in NOD mice with autoimmune diabetes. Combined treatment with EGF (1 mug/kg) and gastrin (3 mug/kg) for 2 weeks restored normoglycemia after diabetes onset in NOD mice, whereas EGF or gastrin alone did not. Fasting blood glucose remained normal (3.5-6.5 mmol/l) or mildly elevated (<11 mmol/l) in five of six mice (83%) for 10 weeks after EGF plus gastrin treatment was stopped, whereas all mice treated with vehicle or EGF or gastrin alone became severely hyperglycemic (12-35 mmol/l). Pancreatic beta-cell mass was increased threefold and insulin content was increased eightfold in mice treated with EGF plus gastrin compared with pretreatment values. The correction of hyperglycemia correlated significantly with increases in pancreatic beta-cell mass and insulin content. In addition, splenic cells from mice treated with EGF plus gastrin delayed diabetes induction by adoptive transfer of diabetogenic cells into immunodeficient NOD-scid mice, suggesting the induction of immunoregulatory cells in NOD mice treated with EGF plus gastrin. We conclude that a short course of combined EGF and gastrin therapy increases pancreatic beta-cell mass and reverses hyperglycemia in acutely diabetic NOD mice; the impact of this combined therapy may result from the effects of EGF and gastrin on beta-cells, immune cells, or both.
 ...
PMID:Combination therapy with epidermal growth factor and gastrin increases beta-cell mass and reverses hyperglycemia in diabetic NOD mice. 1612 47

The precise fate of beta cells and the presence of islet infiltrates after onset of type 1 diabetes have not yet been fully characterized. Recently we showed that in newly diabetic NOD mice an appreciable number of beta cells remain. This was also observed during the first 2 weeks of diabetes in NOD mice without treatment with insulin. However, the mean number of beta cells per unit islet cross-sectional area decreased with increasing duration of disease. In contrast, glucagon and somatostatin cell numbers showed an increase. The persistence of insulitis in several islets until 4 weeks of diabetes suggests ongoing beta cell autoimmunity over a protracted phase. Combined daily treatment of newly diabetic NOD mice with epidermal growth factor (EGF) and gastrin for the first 14 days of diabetes resulted in temporary restoration of normoglycemia in 7 of 15 mice. We speculate that the residual beta cells present soon after onset of diabetes may respond to experimental regeneration. Treatment of newly diabetic NOD mice with the bioactive peptides EGF and gastrin resulted in partial and temporary reversal of diabetes. We propose that peptide therapies combined with other benign immunomodulatory approaches to rescue and preserve beta cells in the long term and to prevent recurring autoimmunity may be more effective than peptide therapy alone in reversing diabetes in NOD mice.
 ...
PMID:Persistence of residual beta cells and islet autoimmunity during increasing duration of diabetes in NOD mice and experimental approaches toward reversing new-onset disease with bioactive peptides. 1912 Feb 89