Epinephrine administration stimulates GLUT4 translocation but reduces glucose transport in muscle.

Epinephrine opposes glucose transport in muscle. Therefore, we investigated the effects of epinephrine administration (25 micrograms/100g body weight) on glucose transport and glucose transporters in rat muscle. Ninety minutes after epinephrine injection 3-O-methyl glucose transport was reduced (approximately 47%) in perfused muscles of the rat hindlimb. Translocation of the insulin-regulatable glucose transporter (GLUT4) in the epinephrine-injected animals was confirmed by the marked increments in the GLUT-4 in the plasma membranes and their concomitant reduction in the intracellular membranes. We speculate a) that it is epinephrine which translocated GLUT4 via a cAMP-linked pathway, and b) that the intrinsic activity reductions are caused either by the glycation of the transporter by the persistent hyperglycemia and/or by epinephrine via the phosphorylation of the GLUT4 transporter protein in muscle.

Glucocorticoid-induced polycystic kidney disease--a threshold trait.

Administration of hydrocortisone acetate (250 mg/kg) to newborn mice caused polycystic kidney disease (PKD) of varying proportions in each of 18 different inbred strains; none of the injected controls were affected. All kidneys were histologically examined and scored for degree of cyst formation using a semi-continuous (0 to 4+) grading scheme. Results suggested that this condition is a multifactorial threshold trait. For each strain, estimates of the mean and standard deviation of normally distributed liability were determined by maximum likelihood methods. Concomitant analyses showed: 1) a significant environmental effect related to drug source; 2) a variation in thresholds ranging from 0.94 (N = 46) for the B10.M strain to -0.71 (N = 297) for the C57B1/6J strain; and 3) three groups of strains with different susceptibility to PKD. These results are consistent with a multifactorial basis for susceptibility to PKD. Quantitative analysis of thresholds and liability distributions reveals that genetic, environmental and random elements all contribute to the expression and extent of the cystic trait.

RU38486 prolongs survival in murine congenital polycystic kidney disease.

The cpk/cpk mutant mouse develops a lethal infantile polycystic kidney disease that is associated with disregulation of post natal glucocorticoid production. To establish if the observed endocrine abnormality is involved in the pathophysiology of polycystic kidney disease, blockade of glucocorticoid action during the immediate post-natal period was attempted. The steroid antagonist, RU38486, when administered from day 3 to day 12 of post-natal life, prolonged survival in affected animals. This finding supports a role for steroid hormones in the pathogenesis of this form of polycystic kidney disease.

Polycystic kidney and liver disease and corticosterone changes in the cpk mouse.

Mice homozygous for the mutation cpk develop a lethal infantile polycystic kidney disease (PKD) and have abnormal elevations of corticosterone in the postnatal period. We examined the development of these elevated glucocorticoid levels in early life. The histological progression of a cystic lesion of the biliary ducts in older heterozygotes was also studied. Normal mice had low (less than 85 nmol/liter) or undetectable (less than 36 nmol/liter) levels from the sixth to twelfth day of life. Corticosterone levels were significantly higher in all homozygote (cpk/cpk) and some of the normal sibs, who were presumed to be heterozygote (cpk/+) mice compared to age-matched controls from day seven to 12. Corticosterone levels were similar from the fifteenth day. A significant proportion of adult obligate heterozygotes from breeding pairs were found to have focal areas of cystic dilatation of the biliary ducts, in the absence of any renal abnormality. The incidence of this lesion increased with age (10% at 150 days, 23% at 300 days, 29% at 450 days, 65% at greater than 450 days of age). The livers of homozygote mice dying in infancy, and control adult mice of the C57BL/6J background strain were free of cysts. The finding of hepatic cysts is reminiscent of adult type PKD. The cpk model thus supports the concept that the different forms of PKD may represent varying expression of a similar gene complex.

The effect of chemical facilitators on the frequency of electrofusion of tobacco mesophyll protoplast.

Trypsin, pronase, protease, dispase, spermine, spermidine, and DMSO were characterized for their effect on the frequency of electrofusion of tobacco mesophyll protoplasts. Protease (Boehringer Mannheim) and Sigma pronase (1.26 mg/ml; 15 min incubation) increased the fusion frequency from 7% (control) to 20.7% (2.9X increase). Following protease and pronase were trypsin (2.8X), spermine (2.4X), dispase (2.1X), DMSO (2.0X), and spermidine (1.4X). BM Protease and polyamines caused the least amount of damage, followed by DMSO and trypsin (26% and 24% decrease in viability respectively), pronase (41%) and dispase (57%). Callus formed from all but dispase-treated protoplasts. Shoots regenerated from calli of all but trypsin-treated protoplasts.