Transgenic expression of gastrin and EGF receptor ligands stimulates islet neogenesis in adult mice, significantly increasing islet mass. The present study aimed to determine whether pharmacological treatment with gastrin and EGF can significantly stimulate b-cell regeneration in chronic, severe insulin-dependent diabetes. Diabetes was induced by intravenous streptozotocin, resulting in ±95% b cell destruction. Four weeks later, blood glucose levels were restored to normal range by exogenous insulin therapy and rats were treated with EGF/gastrin in combination, gastrin alone, or EGF alone given subcutaneously. After 14 days treatment blood glucose was significantly lower in the EGF/gastrin group compared to the untreated diabetic controls. Along with improved glucose tolerance, EGF/gastrin treatment significantly increased plasma C peptide and pancreatic insulin content compared to diabetic controls. Histological analysis showed that EGF/gastrin treatment significantly increased b-cell mass as determined by point counting morphometrics. The EGF/ gastrin group had a significantly greater number of BrdU labelled b-cells/section consistent with stimulation of b-cell replication or neogenesis. An increased number of gastrin receptor positive cells were observed in the EGF/gastrin-treated groups. In contrast to the effectiveness of the EGF/gastrin combination, neither gastrin nor EGF alone improved glucose tolerance in severely streptozotocin-diabetic rats. These studies indicate that physiologically significant improvement in glucose tolerance can be achieved through stimulating b-cell regeneration with gastrin/EGF administered systemically as conventional pharmacological therapy.
La perfusion de protéines dans l’artère rénale du chien entraîne une réduction de la natriurèse du rein ainsi perfusé. Cette diminution de l’excrétion du sodium s’observe indépendamment de toute variation de la filtration glomérulaire. Ce phénomène pourrait constituer un argument en faveur de la conception suivant laquelle une partie, quantitativement non définie, mais sans doute faible, du sodium filtré, serait réabsorbée par un mécanisme de transport passif, dépendant de la grandeur du gradient de pression oncotique existant de part et d’autre de l’épithélium tubulaire.
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