Molecular mechanisms of electrogenic sodium bicarbonate cotransport: structural and equilibrium thermodynamic considerations.

The electrogenic Na(+)-HCO(3)(-) cotransporters play an essential role in regulating intracellular pH and extracellular acid-base homeostasis. Of the known members of the bicarbonate transporter superfamily (BTS), NBC1 and NBC4 proteins have been shown to be electrogenic. The electrogenic nature of these transporters results from the unequal coupling of anionic and cationic fluxes during each transport cycle. This unique property distinguishes NBC1 and NBC4 proteins from other sodium bicarbonate cotransporters and members of the bicarbonate transporter superfamily that are known to be electroneutral. Structure-function studies have played an essential role in revealing the basis for the modulation of the coupling ratio of NBC1 proteins. In addition, the recent transmembrane topographic analysis of pNBC1 has shed light on the potential structural determinants that are responsible for ion permeation through the cotransporter. The experimentally difficult problem of determining the nature of anionic species being transported by these proteins (HCO(3)(-) versus CO(3)(2-)) is analyzed using a theoretical equilibrium thermodynamics approach. Finally, our current understanding of the molecular mechanisms responsible for the regulation of ion coupling and flux through electrogenic sodium bicarbonate cotransporters is reviewed in detail.

In vitro effects of insulin on aldosterone production in rat zona glomerulosa cells.

Though long standing diabetes mellitus is frequently accompanied by hypoaldosteronism, the role of insulin in this setting has never been clearly established. In the present study we have examined the direct effects of insulin on aldosterone production in rat zona glomerulosa cells in vitro. Insulin is shown to directly stimulate aldosterone production in a dose dependent manner, and to attenuate angiotensin II mediated aldosterone production, without affecting angiotensin II receptor binding kinetics. Insulin had no effect on aldosterone production mediated by the other physiological stimuli (K+ and ACTH). These data suggest a possible interaction between insulin and angiotensin II in the regulation of aldosterone secretion.

Diabetes mellitus in elderly nursing home patients. A survey of clinical characteristics and management.

The clinical features of 47 frail nursing home diabetic patients with a mean age of 81 +/- 1.6 years were compared to those of 61 nondiabetic nursing home residents with a mean age of 80.2 +/- 1.2 years. Diabetic patients had a higher prevalence of renal failure, proteinuria, retinopathy, neuropathy, and infections than did other nursing home residents. Macroangiopathic disease tended to be equally common in both age groups. Diabetic nursing home residents had higher body weights compared to nondiabetic nursing home residents. Surprisingly, however, 21% of nursing home diabetics were greater than 20% below average body weight (compared to 24.5% of other nursing home residents), suggesting that undernutrition is a major problem in diabetic patients in a nursing home setting. Overall, the diabetic nursing home patients had better blood glucose control than younger ambulatory diabetic patients (mean age 66.2 +/- 4.7 years). The glycosylated hemoglobin (HbA1) level in those on oral agents was 8.9% +/- 0.7% for nursing home patients compared to 11.8% +/- 0.7% in ambulatory patients (P less than 0.01). The HbA1 in insulin-treated patients was similarly lower in nursing home diabetics (9.6% +/- 0.4% vs 11.8% +/- 0.7, P less than 0.05). There were only two mild hypoglycemic episodes in nursing home patients over 6-month observation period, whereas 12 ambulatory patients reported hypoglycemic episodes during the same period of time. We conclude that although the diabetic nursing home patients are sicker than the ambulatory diabetics, it is possible to achieve a fair blood glucose control in nursing home patients without a significant risk of recurrent hypoglycemia.

Cyclosporin A-induced hyperreninemic hypoaldosteronism. A model of adrenal resistance to angiotensin II.

We studied the effects of cyclosporin A on the renin-aldosterone axis in Sprague-Dawley rats. Two weeks of intragastric administration of cyclosporin A (5 mg/kg/day or or 20 mg/kg/day) resulted in large increases in plasma renin concentration (23 +/- 5, 70 +/- 12, and 79 +/- 11 ng/ml/hr in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively), with no parallel increments in plasma aldosterone. In vitro angiotensin II (ANG II)-stimulated aldosterone secretion by zona glomerulosa cells obtained from cyclosporin A-treated rats was also reduced (4.8 +/- 0.5, 1.5 +/- 0.2, and 0.2 +/- 0.2 ng/10(5) cells in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively). In contrast, in vitro aldosterone response to graded increments of potassium (3.7-10.7 mmol/L) or adrenocorticotropic hormone (ACTH) (10(-11)-10(-8) M) was preserved in cyclosporin A-treated rats. When added in vitro to zona glomerulosa cells from untreated rats, cyclosporin A also attenuated ANG II-stimulated aldosterone secretion, but did not affect potassium or ACTH-mediated aldosterone production. Thus, cyclosporin A-induced hyperreninemic hypoaldosteronism in the rat depends on opposing renal and adrenal effects, with a direct or feedback stimulation of renin secretion and a specific blockade of ANG II-mediated aldosterone production.