Phosphoinositide metabolism and insulin secretion from isolated rat pancreatic islets.

Clements, Rex S.; Rhoten, William B.

doi:10.1172/jci108325

Cited by 88 publications

(60 citation statements)

References 34 publications

(43 reference statements)

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“…First, 3H-inositoi is exclusively incorporated into inositol-containing phospholipids [20,21]. Second, an increase in perifusate 3H is paralleled by a decrease in labelled inositol-containing phospholipids [20].…”

Section: Discussionmentioning

confidence: 99%

Time-dependent potentiation of insulin release induced by alpha-ketoisocaproate and leucine in rats: possible involvement of phosphoinositide hydrolysis

Zawalich

1988

Diabetologia

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Summary. The ability of the amino acid leucine and its keto acid, alpha-ketoisocaproate, to induce insulin release, to initiate phosphoinositide hydrolysis, and to amplify the subsequent insulin secretory response to glucose was assessed. In islets whose inositol-containing lipids were prelabelled with myo [2-3H]inositol, the addition of either compound resulted in an increase in insulin output, an increase in 3H effiux, rapid and significant increases in labelled inositol phosphate accumulation and a sustained increase in 3H efflux after removal of the stimulant. Direct measurements of labelled inositol phosphate accumulation in islets previously stimulated with alpha-ketoisocaproate demonstrate that this sustained increase in ~H effiux was the result of a persistent increase in phosphoinositide hydrolysis and was not simply a consequence of the hydrolysis of preformed inositol phosphates into more membrane permeable species. Prior exposure of islets to alpha-ketoisocaproate or leucine also resulted in an amplified secretory response to a subsequent glucose (10 mmol/1) stimulus. While peak first phase insulin release averaged 66+_4 (mean +_ SEM, n=18) pg.islet -1. min -1 from control islets, this value increased to 204+_14 and 246_+ 11 pg. islet-1. min-1 in the leucine or alpha-ketoisocaproate pretreated islets respectively. The duration of this amplified response paralleled the duration of the persistent increase in 3H effiux. Prior alpha-ketoisocaproate exposure also amplified the subsequent insulin secretory response to tolbutamide and glyceraldehyde. While control (non-pretreated) islets in response to tolbutamide (200 I.tmol/l) released insulin at a rate of 50+6 pg.islet-l.min -1 (n=3), this first phase response increased to 506+_38 pg.islet -lrain -1 in prior alpha-ketoisocaproate treated islets. Peak first and second phase insulin responses to glyceraldehyde were increased 5-fold and 2-fold, respectively, by prior alpha-ketoisocaproate. These results suggest that events coupled to the hydrolysis of membrane inositol-containing phospholipids induced by leucine and alpha-ketoisocaproate participate not only in their acute insulin stimulatory action, but also in their ability to induce time-dependent potentiation (memory) in isolated islets.Key words: Islets, phosphoinositides, memory, insulin secretion, leucine, alpha-ketoisocaproate, 3H efflux.It is well established that prior glucose stimulation of pancreatic B cells results in an amplified insulin secretory response to a second glucose challenge [1][2][3][4]. Some characteristics of this phenomenon, termed timedependent potentiation (TDP) by Grill and associates [2,3] have been established: (a) glucose must be metabolised to induce TDP; (b)TDP develops within minutes and persists long after removal of the initial stimulant; (c)intracellular accumulation of cAMP does not seem to play a major role in the process; and (d) glyceraldehyde and the gut hormone cholecystokinin [5] mimic to a large extent this sensitising effect of glucose. We recently reported ...

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Section: Discussionmentioning

confidence: 99%

Time-dependent potentiation of insulin release induced by alpha-ketoisocaproate and leucine in rats: possible involvement of phosphoinositide hydrolysis

Zawalich

1988

Diabetologia

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“…A large amount of data indicates that PIP 2 plays an important role in the insulin secretory process. It was recognized early that the rate of phosphoinositide metabolism is increased in glucose-stimulated islets (8,9). This effect is due to PLC-mediated hydrolysis of PIP 2 (10).…”

mentioning

confidence: 99%

Rapid Turnover of Phosphatidylinositol-4,5-Bisphosphate in Insulin-Secreting Cells Mediated by Ca2+ and the ATP-to-ADP Ratio

2007

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P hosphatidylinositol 4,5-bisphosphate (PIP 2 ) is a minor membrane component of eukaryotic cells constituting ϳ1% of the phospholipids in the inner leaflet of the plasma membrane. Nevertheless, the phospholipid plays important roles in the regulation of a variety of cell functions. Apart from serving as a precursor for the messenger molecules inositol-1,4,5-trisphosphate (IP 3 ) and diacylglycerol generated on activation of phospholipase C (PLC) (1), and for phosphoinositide 3-kinase-generated phosphatidylinositol-3,4,5-trisphosphate (2), PIP 2 is known to regulate ion channel activity (3), proteins involved in organization of the cytoskeleton (4), and the trafficking of vesicles in endo-and exocytosis (5). PIP 2 is mainly synthesized in two steps by phosphorylation of phosphatidylinositol to phosphatidylinositol-4-phosphate (PIP) by phosphatidylinositol 4-kinases (PI 4-kinases), followed by PIP phosphorylation to PIP 2 by type I PIP 5-kinases (6). Some PIP 2 is also formed via phosphorylation of phosphatidylinositol-5-phosphate by type II PIP 4-kinases (6).Pancreatic ␤-cells secrete insulin after elevation of the ambient glucose concentration. The rapid uptake and metabolism of the glucose lead to an increase of the intracellular ATP-to-ADP ratio, closure of ATP-sensitive K ϩ channels (K ATP channels) in the plasma membrane, depolarization, and opening of voltage-dependent Ca 2ϩ channels. The resulting increase of the cytoplasmic Ca 2ϩ concentration ([Ca 2ϩ ] i ) triggers exocytosis of insulin secretory granules (7). A large amount of data indicates that PIP 2 plays an important role in the insulin secretory process. It was recognized early that the rate of phosphoinositide metabolism is increased in glucose-stimulated islets (8,9). This effect is due to PLC-mediated hydrolysis of PIP 2 (10). However, there are different opinions about the mechanisms underlying glucose-induced PLC activation. Whereas several studies indicate that the glucoseinduced phosphoinositide hydrolysis depends on the presence of extracellular Ca 2ϩ (9,11,12), other reports indicate that the process is at least in part Ca 2ϩ independent (13-15). Recent observations in single insulinoma cells (16) and intact mouse islets (17) have demonstrated that elevation of [Ca 2ϩ ] i is sufficient to trigger PLC activity and that [Ca 2ϩ ] i oscillations are associated with periodic activation of PLC. However, the kinetics of the early changes in PIP 2 concentration and how it is related to [Ca 2ϩ ] i after glucose stimulation are unknown. PIP 2 has been found to be important for secretion independent of its role as substrate for PLC. A role for PIP 2 in exocytosis was first suggested by the observation that phosphatidylinositol transfer protein and a type I PIP 5-kinase are essential components of the ATP-dependent priming of exocytotic vesicles in permeabilized chromaffin cells (18,19). The importance of PIP 2 was later confirmed by experiments showing that exocytosis is negatively affected by inhibition of PIP 2 synthesis in various type...

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“…Phosphatidylinositol (PI) turnover is increased during secretory activity of the thyroid (7), adrenal medulla (8), exocrine pancereas (9-11), and islets of Langerhans (12). Recently, it has been reported by Lo et al (13) In these investigations we have characterized the renal clearance and metabolism of MI in the isolated dog kidney.…”

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confidence: 99%

Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys

Molitoris¹,

Hruska

Fishman

et al. 1979

J. Clin. Invest.

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A B S T R A C T The effects of glucose and parathyroid hormone (PTH) on the transport and metabolism of myoinositol (MI) and [2-3H] 1110 release were about coincidental with the increase in urinary cyclic 3',5'-AMP after PTH and preceded the peak phosphaturic effect of PTH. There was no detectable effect of PTH on MI synthesis from glucose as a source of the MI released into the urine and perfusate. However, PTH temporarily halted accumulation of tritiated MI catabolites. There was no effect of inactivated PTH on urinary cyclic 3',5'-AMP or on MI transport, which indicates that the PTH effect on MI handling was a specific hormonal effect. These studies clarify the renal metabolism of MI, and they demonstrate heretofore unknown effects of PTH on the renal handling and metabolism of MI. The effects of PTH on renal MI metabolism have important implications in renal carbohydrate metabolism and phospholipid turnover.

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Phosphoinositide metabolism and insulin secretion from isolated rat pancreatic islets.

Cited by 88 publications

References 34 publications

Time-dependent potentiation of insulin release induced by alpha-ketoisocaproate and leucine in rats: possible involvement of phosphoinositide hydrolysis

Time-dependent potentiation of insulin release induced by alpha-ketoisocaproate and leucine in rats: possible involvement of phosphoinositide hydrolysis

Rapid Turnover of Phosphatidylinositol-4,5-Bisphosphate in Insulin-Secreting Cells Mediated by Ca2+ and the ATP-to-ADP Ratio

Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys

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