J. C. Basabe

Action of sex hormones on the insulinemia of castrated female rats.

Summary Castrated female rats received daily subcutaneous injections of progesterone (500 μg/day), testosterone (500 μg/day), and 17 β-estradiol (4 μg/day) for 7 months. Lower fasting blood sugar values were found in the 17 β-estradiol-treated group after 6 and 7 months of treatment. The plasma immunoreactive insulin level was augmented by the sixth month of treatment in the testosterone treated group and by the second, fifth, sixth, and seventh months of treatment in the 17 β-estradiol group.

Secretion and effect of somatostatin in early stages of the diabetic syndrome in C57BL/KsJ-mdb mice

SummaryIn a previous study in C57BL/KsJ (mdb) mice aged 12 to 90 days, we observed alterations in the secretion of insulin and somatostatin and in the inhibitory effect of the latter upon insulin secretion. This study explores whether hormonal alterations are to be found in the very early stages of the diabetic syndrome, i. e. between ages 4 and 12 days. The results demonstrate two distinct phases in the development of the syndrome: (a) up to age 6 days, the perifused slices of pancreata of control animals present biphasic glucose-induced patterns of insulin and somatostatin secretion, whereas the diabetic animals show a diminished first peak of insulin secretion, but a similar pattern of somatostatin secretion, to that of the control animals; (b) between ages 7 and 12 days, the pancreata of diabetic mice exhibit insulin hypersecretion in basal conditions, and an absence of the first secretion peak and insulin hypersecretion in the second phase in response to glucose stimulation. The glucose-induced pattern of somatostatin secretion presents hormonal hypersecretion in both phases. B-cell sensitivity to the inhibitory effect of somatostatin is diminished in mdb mice of the above-mentioned groups, an alteration which becomes more evident as diabetes evolves. The results show that, in very early stages of the evolution of the diabetic syndrome in C57BL/KsJ (mdb) mice, there are already alterations in insulin and somatostatin secretion patterns and in the inhibitory effect of the latter on insulin secretion.

Studies on carbohydrate metabolism in penguins (Pygocellis papua)

Abstract The present experiment was performed in the Antartic continent at 64° 53′ S Lat; 62° 53′ W Long. Gento penguins ( Pygocellis papua ) were studied after 24–48 hr and 6–12 days of starvation. After intravenous injection of glucose (1 g/kg), the blood sugar levels remained elevated for periods up to 10 hr. Starvation did not affect the glucose tolerance curve. The pancreatic function was tested using hipoglycemic agents. Tolbutamide (200 mg/kg) and chlorpropamide (100 mg/kg) did not induce any changes in the blood sugar level. Inmunoreactive serum insulin level was about 40 μU/ml after 24–48 hr of starvation. This value fell to about 10 μU/ml after 12 days of starvation. Intravenous glucose injection was without significant effect in insulin secretion.

In vitro insulin secretion from the penguin (Pygoscelis papua) pancreas

Abstract In experiments performed at the Almirante Brown Scientific Station (64° 53′ South; 62° 53′ West), arginine induced in penguins significant release of insulin from incubated pieces of pancreas, while glucose acted as stimulus only at very high concentrations. Substances active on the adenyl cyclase system, such as glucagon, theophylline, isoproterenol, and even 3′,5′ cyclic AMP, stimulated insulin release. l -Propranolol inhibited isoproterenol-induced insulin release. Phentolamine, in the doses used, had no effect on either basal or isoproterenol-induced insulin secretion. Ouabain and glibenclamide failed to promote any change in the amount of insulin secreted. The results suggest that (a) in the penguin pancreas arginine rather than glucose may be a prominent stimulus for insulin secretion; (b) the penguin beta cell shows decreased sensitivity to glucose; (c) the adenyl cyclase system plays an important role in the mechanism(s) regulating insulin secretion; (d) under our experimental conditions, adrenergic modulation of insulin release is mediated chiefly through beta receptors.

Effect of cephalic glucose infusion on insulin secretion.

SumaryThe continous infusion of glucose (1 mg/kg/min) via the carotid artery in anesthetized dogs produces a biphasic pattern of insulin secretion. The first peak reaches a maximum 3 min after glucose infusion and drops to basal level at 7 min. As long as the glucose infusion persists a slow and mantained increase in insulin level in the pancreaticoduodenal vein can be observed. The same amount of glucose infused in the general circulation via the jugular vein provoked a different pattern of insulin secretion. Cerebral glucose infusion to vagotomized dogs also produced a two phase response in insulin secretion, but the levels reached in the first phase were lower that those observed in the normal dogs. The infusion of glucose, via the jugular vein, in vagotomized dogs, failed to induce any change in plasma insulin levels. Our data suggest that a glucose load to the brain induces pancreatic insulin secretion mediated partially by the vagus nerves. These results are also compatible with the hypothesis that a humoral factor could be involved in the pancreatic response.

Aspects of intermediary metabolism and insulin level in the penguin (Pygocellis papua)

The present experiment was performed in the Antartic continent at 64° 53′ S Lat.; 62° 53′ W Long. The following studies were carried out in the Gentoo penguins (Pygocellis papua). A—Pancreatic response to intravenous injection of arginine and phenformin. B—Changes in blood sugar levels, urea, and uric acid induced by the intravenous injection of arginine and phenformin. C—Changes in blood sugar levels elicited by the injection of porcine crystalline insulin. Intravenous injection of arginine raised the plasma immunoreactive insulin (IRI) 5 and 15 min after its administration. Phenformin failed to induce any modification in the circulating level of IRI. Plasma urea and uric acid levels were found to be elevated after arginine injection. The injection of phenformin did not modify the plasma urea level, increased the plasma uric acid values and lowered the blood sugar levels. Crystalline insulin lowered the blood sugar level. The same effect was observed when insulin was injected after 13 days of starvation.

Effect of Modified Diabetic Splenocytes on Mice Injected with Splenocytes from Multiple Low-Dose Streptozotocin Diabetic Donors

Etiological agents of autoimmune processes that have been made nonvirulent by several treatments, i.e., mitomycin C (Mit C), can be used as a vaccine to protect against disease. In this work we studied the effects of splenocytes from diabetic mice on animals that had been injected with modified splenocytes (Mit C-treated splenocytes from multiple low-dose streptozotocin [mld-sz] mice) 15 days before. Splenocytes from mld-sz diabetic donors altered i.p. glucose tolerance and the first peak of insulin secretion pattern when injected into normal singeneic recipients. These effects can be prevented partially (one injection in a vaccine form) or completely (two injections with a 15-day interval) by a previous injection of Mit C-treated mononuclear splenocytes (MS) from mld-sz mice. The fact that control splenocytes previously treated with Mit C were not able to achieve similar results indicates that donor splenocytes have to be diabetic to prevent the disease. On the other hand, Mit retreated diabetic MS were not effective in preventing the alterations in glucose tolerance and in the pattern of insulin secretion when injected into athymic mice. This suggests that the preventive effect of Mit C-treated diabetic MS injection also implies an active role of the T cells from the recipient mice. Mit C-treated diabetic splenocytes are preferentially trapped by the pancreas and the lymph nodes from recipient mice. Our results show that the impairment in glucose tolerance and in the insulin secretion pattern produced by diabetic splenocyte transfer can be prevented by one or two previous injections of Mit C-modlfied diabetic splenocytes.

Is Lipotoxicity presents in the early stages of an experimental model of autoimmune diabetes? Further studies in the multiple low dose of streptozotocin model

An increased availability of plasma free fatty acids (FFA) seems to play a role in the early stages of experimental type 1 diabetes mellitus induced in C57BL/6J mice by multiple low doses of streptozotoxin (mld-STZ). We analyzed the temporal changes of: (1) plasma and skeletal muscle lipids and their relationship with glucose metabolism; (2) triglyceride (Tg) concentration in isolated islets; (3) intraperitoneal glucose tolerance test; and (4) insulin secretion patterns when the three mutually interactive glucose signaling pathways were activated. Animals were killed by cervical dislocation at days 4, 6, 7, 8, 9 and 12 post first injection of mld-STZ. Compared with control mice, we observed: (1) at day 6, a significant increase of plasma FFA and both muscle and islet Tg content and a significant decrease of muscle pyruvate dehydrogenase activity. These parameters further deteriorated with time. (2) plasma Tg, glucose and insulin levels and glucose tolerance test were significantly different only after day 8. (3) an increase in both phases of the glucose plus palmitate-stimulated insulin secretion was observed at day 4. This effect progressively decreased since day 7 up to day 9. Moreover, an inhibitory action of cerulenin over glucose plus palmitate-stimulated insulin secretion was observed between days 6 and 9. Taken together these results suggest that early alteration in carbohydrate and lipid metabolism could represent a “metabolic window” which would develop between days 6 and 8. Afterwards, subsequent immunological alterations, apoptosis and necrosis induced the destruction of β cells and would mask the results mentioned above.

First phase of insulin secretion stimulated by glucose plus theophylline and inhibitory effect of somatostatin in genetically diabetic mice (C57BL/KsJ-mdb)

SummaryIn a previous study in C57BL/KsJ mdb/mdb mice aged 4 to 12 days we observed a diminished first phase of glucose-induced insulin secretion in vitro, and alterations in the inhibitory effect of somatostatin on insulin secretion. This study explores, using perifused pancreatic slices, whether the reduced B-cell responsiveness to somatostatin in mdb/mdb mice can be overcome upon induction of a biphasic insulin release by using theophylline. Under these conditions our results show: (1) in mdb/mdb mice aged 4 to 6 days, the restoration of the first peak of insulin secretion overcomes the resuced B-cell sensitivity to somatostatin; and (2) in mdb/mdb mice aged 7 to 12 days, the addition of theophylline only causes a partial restoration of B-cell responsiveness to somatostatin, suggesting that other mechanisms could be involved in the progressive impairement of B-cell sensitivity to somatostatin inhibitory effect.