Acute pretreatment with pyrazole and ethanol: effects on glucose-induced changes in insulin and glucagon

Ethanol suppressed, in a dose-related manner, glucose-induced insulin (IRI) release and thus delayed the disappearance of glucose from the blood of rats. Pretreatment with pyrazole, an alcohol dehydrogenase inhibitor, exacerbated the effect of ethanol on IRI release, glucose tolerance and glucagon (IRG) release. These results suggest that ethanol produces glucose intolerance by inhibiting glucose-induced IRI release and by augmenting IRG release. Moreover, these findings indicate that ethanol does not have to be metabolized completely in order to produce these effects.     

Adrenergic receptors and secretory responses of the rat submandibular salivary gland after periodic incisor reduction

While loss-of-function mutations in Gsalpha are invariably associated with the short stature and brachydactyly of Albright hereditary osteodystrophy (AHO), the association with hormone resistance (to parathyroid hormone and thyrotropin) typical of pseudohypoparathyroidism type Ia (PHP-Ia) is much more variable. Observational studies and DNA polymorphism analysis suggest that maternal transmission of the Gsalpha mutation may be required for full expression of clinical hormone resistance. To test this hypothesis, we studied transmission of a frameshift mutation in Gsalpha through three generations of a pedigree affected by AHO and PHP-Ia. While all family members carrying this loss-of-function mutation in one Gsalpha allele had AHO, neither the presence of the mutation nor the degree of reduction of erythrocyte Gsalpha bioactivity allowed prediction of phenotype (AHO alone versus AHO and PHP-Ia). Paternal transmission of the mutation (from the patriarch of the first generation to three members of the second generation) was not associated with concurrent PHP-Ia, but maternal transmission (from two women in the second generation to four children in the third generation) was invariably associated with PHP-Ia. No expansion of an upstream short CCG nucleotide repeat region was detected, nor was there evidence of uniparental disomy by polymorphism analysis. This report, the first to document the effects across three generations of both paternal and maternal transmission of a specific Gsalpha mutation, strongly supports the hypothesis that a maternal factor determines full expression of Gsalpha dysfunction as PHP-Ia.