Insulin Release in Pregnancy: Studies on Adenylate Cyclase, Phosphodiesterase, Protein Kinase, and Phosphoprotein Phosphatase in Isolated Rat Islets of Langerhans*

SUMMARY The effects of hypophysectomy and short-term GH replacement on insulin release and on some aspects of glucose metabolism in isolated rat islets of Langerhans were investigated. The effects on body, pancreas and adrenal gland weights, and on the levels of blood plasma constituents were also measured. Three to four weeks after hypophysectomy the early and late phases of insulin release from islets incubated with high concentrations of glucose, but not with low concentrations of glucose or with xylitol, leucine, arginine, tolbutamide, citrate or butyrate, were significantly lowered. Short-term GH replacement partially reversed the depression in glucose-stimulated insulin release. This reversal effect was not dependent on the increase in body weight of rats after GH replacement when the fall in adrenal gland but not in pancreas weight was also reversed. Nine out of the 12 plasma constituents measured, including glucose, were maintained in the control range of levels, but albumin, inorganic phosphate and urea nitrogen levels were altered after hypophysectomy or GH replacement. Three to four weeks after hypophysectomy, total glucose oxidation and glucose utilization by the islets were slightly depressed. Hypophysectomy appeared to slow down glucose 6-phosphate utilization in the islets. However, the functional capacity of the glucose phosphorylating, glucose-6-phosphate and 6-phosphogluconate dehydrogenase activities were not changed. Short-term GH replacement caused improvements in these islet functions.

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Evidence That Cholecystokinin Interacts with Specific Receptors and Regulates Insulin Release in Isolated Rat Islets of Langerhans

Diabetes ◽

10.2337/diab.35.1.38 ◽

1986 ◽

Vol 35 (1) ◽

pp. 38-43 ◽

Cited By ~ 44

Author(s):

E. J. Verspohl ◽

H. P. T. Ammon ◽

J. A. Williams ◽

I. D. Goldfine

Keyword(s):

Insulin Release ◽

Islets Of Langerhans ◽

Rat Islets ◽

Isolated Rat Islets ◽

Specific Receptors ◽

Rat Islets Of Langerhans ◽

Isolated Rat

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Alterations in regulation of insulin biosynthesis in pregnancy and starvation studied in isolated rat islets of Langerhans

Biochemical Journal ◽

10.1042/bj1660501 ◽

1977 ◽

Vol 166 (3) ◽

pp. 501-507 ◽

Cited By ~ 10

Author(s):

Adrian J. Bone ◽

Simon L. Howell

Keyword(s):

Cyclic Amp ◽

Islets Of Langerhans ◽

Insulin Biosynthesis ◽

Normal Female ◽

Pregnant Rats ◽

Rat Islets ◽

Isolated Rat Islets ◽

Rat Islets Of Langerhans ◽

Isolated Rat ◽

In Pregnancy

1. Insulin biosynthesis in isolated rat islets of Langerhans was determined by the incorporation of [3H]leucine into newly synthesized islet proteins. Anti-insulin serum covalently coupled to a solid phase (CNBr-activated Sepharose 4B) was used to separate the immunoreactive proinsulin and insulin from other islet proteins. This method was applied to a study of the regulation of insulin biosynthesis in isolated rat islets of Langerhans during pregnancy, and immediately after a period of food deprivation. 2. Islets isolated from pregnant rats showed an increased basal rate of synthesis compared with the non-pregnant controls. In addition, they showed a significant increase in biosynthesis of proinsulin and insulin in comparison with the normal islets over a range of glucose concentrations of 2–20mm. 3. Addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine significantly increased the insulin-synthetic response of normal islets over the glucose range 5–20mm, so that their glucose response approached that of islets from pregnant rats. 4. Normal female rates were injected with a long-acting progesterone derivative (hydroxyprogesterone hexanoate), to investigate the role of progesterone on the increased insulin biosynthesis observed in islets in pregnancy. There appeared to be no marked difference in insulin biosynthesis between the islets from the progesterone-injected and control rats in the presence of 2mm- or 6mm-glucose alone. However, in the presence of 4mm- or 6mm-glucose and 3-isobutyl-1-methylxanthine there was a significant increase in insulin biosynthesis in the progesterone-treated animals. 5. Total islet protein biosynthesis was determined by the incorporation of [3H]leucine into trichloroacetic acid-precipitable islet proteins. Islets isolated from normal rats showed a 1.6-fold increase in incorporation over the glucose concentration range 2–20mm, and this value remained unchanged during starvation; however, rates of incorporation were significantly raised in islets isolated from pregnant rats in the presence of 20mm-glucose. 6. Islets from starved and fed control rats were incubated in the presence of increasing concentrations of glucose or glucose+3-isobutyl-1-methylxanthine. The islets isolated from the starved animals showed a diminished insulin-synthetic response to glucose as compared with the controls; this response was partially restored to normal values by elevation of cyclic AMP concentrations by using 3-isobutyl-1-methylxanthine. 7. It is suggested that the alterations in glucose-stimulated insulin biosynthesis observed in islets during pregnancy and after a period of starvation could be attributable, at least in part, to a long-term alteration of the cyclic AMP system, and in pregnancy to a direct or indirect effect of progesterone on β-cell function.

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Pentitols and insulin release by isolated rat islets of Langerhans

Biochemical Journal ◽

10.1042/bj1090333 ◽

1968 ◽

Vol 109 (3) ◽

pp. 333-339 ◽

Cited By ~ 72

Author(s):

W Montague ◽

K W Taylor

Keyword(s):

Insulin Release ◽

Islets Of Langerhans ◽

Pentose Phosphate ◽

Rat Islets ◽

Isolated Islets Of Langerhans ◽

Isolated Rat Islets ◽

Rat Islets Of Langerhans ◽

Stimulate Insulin Release ◽

Isolated Rat

1. Insulin secretion was studied in isolated islets of Langerhans obtained by collagenase digestion of rat pancreas. In addition to responding to glucose and mannose as do whole pancreas and pancreas slices in vitro, isolated rat islets also secrete insulin in response to xylitol, ribitol and ribose, but not to sorbitol, mannitol, arabitol, xylose or arabinose. 2. Xylitol and ribitol readily reduce NAD+ when added to a preparation of ultrasonically treated islets. 3. Adrenaline (1μm) inhibits the effects of glucose and xylitol on insulin release. Mannoheptulose and 2-deoxy-glucose, however, inhibit the response to glucose but not that to xylitol. 4. The intracellular concentration of glucose 6-phosphate is increased when islets are incubated with glucose but not with xylitol, suggesting that xylitol does not promote insulin release by conversion into glucose 6-phosphate. 5. Theophylline (5mm) potentiates the effect of 20mm-glucose on insulin release from isolated rat islets of Langerhans, but has no effect on xylitol-mediated release. These results indicate that xylitol does not stimulate insulin release by alterations in the intracellular concentrations of cyclic AMP. 6. A possible role for the metabolism of hexoses via the pentose phosphate pathway in the stimulation of insulin release is discussed.

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