Hormonal regulation of gluconeogenesis in cultured proximal tubular cells: role of cytosolic calcium.
Gluconeogenic competence of primary cultures of canine renal proximal tubular cells has been examined. Cells grown in 5 mM glucose media or in glucose-free media exhibited pyruvate-stimulated glucose production, as opposed to cells grown in 20 mM glucose media. By 72 h after the last media change, confluent cells grown in 5 mM glucose medium turn from a predominantly glycolytic to an oxidative type of metabolism. By this time, glucose production exhibited pH, 3-mercaptopicolinate, and insulin sensitivity. Parathyroid hormone, angiotensin II, and phenylephrine stimulated glucose production in a nonadditive fashion. Single-cell cystolic Ca2+ measurements using microspectrofluorometric techniques revealed that all three hormones elicited Ca2+ transients in proximal tubular cells. Ionomycin stimulated glucose production by proximal tubular cells, suggesting that Ca2+ transients could represent a sufficient stimulus for glucose production. When hormone-induced Ca2+ transients were curtailed by a pretreatment with the membrane-permeant Ca2+ chelator, Maptam, hormonal stimulation of glucose production was abolished, suggesting that Ca2+ transients represent not only a sufficient, but a necessary event in the stimulation of glucose production by these hormones.
Renal Division, Jewish Hospital of St. Louis, Missouri.
M S
MS
Goligorsky
D
D
Osborne
T
T
Howard
K A
KA
Hruska
I E
IE
Karl
D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005943:Gluconeogenesis; D006728:Hormones / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology
D006728:Hormones; D010281:Parathyroid Hormone; D000804:Angiotensin II; D010656:Phenylephrine; D000255:Adenosine Triphosphate; D010695:Phlorhizin; D002118:Calcium