The rapid adjustment of renal sodium excretion to changes in dietary sodium intake in sheep

The rapidity with which the kidney alters sodium excretion (ENa) in response to changes in dietary Na was studied in Merino sheep by analyzing hourly ENa for three control days, and then for three days after a change in Na intake. On a control diet of 117 mmol Na, sheep had a pre-feeding ENa of 3.5 mmol/hr., a striking post-feeding natriuresis that began 2 hours after feeding (less than 0.01), peaked at 4 hrs. and then declined to pre-feeding levels 7 hrs. after feeding. When in balance on a high Na diet the feeding of a low Na meal resulted in marked depression of ENa within 4 hours after feeding. On a low Na diet, a 100 mmol Na meal resulted in an increase in ENa within 4 hours but a 50 mmol Na meal did not. Thus, the sensitivity of post-feeding natriuresis is between 50 and 100 mmols Na. As post feeding natriuresis is a naturally occurring physiological event it should provide a useful paradigm for the investigation of mechanisms controlling Na balance.     

Treatment of Severe Diabetes Mellitus by Insulin Infusion

A new and simple form of insulin therapy for diabetic hyperglycaemia and ketoacidosis has been developed using a continuous intravenous infusion of insulin at a rate of 2·4 U/hr to maintain serum insulin concentration at physiological levels. This rate raises the mean serum insulin to 83 μU/ml and has a therapeutic effect which is not augmented by higher infusion rates. The response to such low doses of insulin indicates a need for a reappraisal of currently held theories about insulin resistance in diabetic ketoacidosis. In 11 diabetic patients with a mean plasma glucose of 514 mg/100 ml this therapy produced continuous falls in plasma glucose at a mean rate of 75 mg/100 ml/hr, and 10 out of 11 patients recovered within eight hours. This form of therapy is simple to institute, not complicated by hypoglycaemia, and avoids the confusion and empiricism of previously described forms of therapy.     

Elevation of plasma triglyceride levels due to 2-deoxy-D-glucose in conscious rats

Hypertriglyceridemia due to 2-deoxy-D-glucose administration was observed in conscious rats. Plasma triglyceride levels were elevated dose-dependently 2 or 3 hrs after administration of 2-deoxy-D-glucose (5-40 mg/100 g body weight). Prior to the rises in triglyceride, plasma epinephrine levels were elevated rapidly, whereas plasma insulin was not increased depspite continuous hyperglycemia. Elevation of plasma triglyceride was suppressed by addition of phentolamine, whereby insulin release was remarkably enhanced. Plasma lipoprotein lipase release by heparin infusion was significantly suppressed 2 hr after 2-deoxy-D-glucose administration. In conclusion, it is suggested that the hypertriglyceridemic effect of 2-deoxy-D-glucose may be mediated by decreased clearance of endogeneous lipoprotein particles (mostly chylomicrons) attributable to a lowered lipoprotein lipase activity.     

FSH and LH variations in beef cows during the postpartum period

To study the plasma gonadotrophin profiles of 9 cows after parturition, blood samples were obtained every 20 min for 12 hrs on three occasions between 5 and 50 days postpartum and analysed by RIA techniques. The time of the first ovulation, as judged by plasma progesterone levels, varied from 30 to more than 60 days postpartum. Variations in mean levels of FSH and LH were not significantly correlated with the postpartum interval. However, the mean levels of plasma FSH and number of LH pulses were lower in females which had not ovulated than in those which had. The cows could be classified into four groups: group 1 with less than 4 LH pulses in 12 hrs and a mean plasma FSH level less than 138 ng/ml; group 2 with more than 4 LH pulses in 12 hrs and varying plasma FSH levels; group 3 with less than 4 LH pulses in 12 hrs and a mean plasma FSH level greater than 138 ng/ml; group 4 which had ovulated. This classification indicated that the LH and FSH levels progressed significantly (2.46 to 3.56 ng/ml, P less than 0.05; 120 to 159 ng/ml, P less than 0.01, respectively) from groups 1 to 3, and that they decreased in the females which had ovulated (group 4). Since the time of the first ovulation after parturition varied, it was not possible to demonstrate any relationship between that interval and the mean plasma gonadotrophin profiles. However, when ovulation was considered as time zero there was a clear increase in plasma gonadotrophin before ovulation.     

Diurnal Variation in Response to Intravenous Glucose

Intravenous glucose tolerance tests (25 g) were performed in the morning and afternoon on 13 apparently normal persons. The individual K values (rate of decline of blood sugar) were all higher in the morning tests, and the mean values were significantly higher in the morning. Fasting blood sugar levels were slightly lower in the afternoon. There was no difference between the fasting morning and afternoon plasma insulin levels, but the levels after glucose were lower in the afternoon. Growth hormone levels were low at all times in non-apprehensive subjects and unaffected by glucose. The results suggest that the impaired afternoon intravenous glucose tolerance, like oral glucose tolerance, is associated with impaired insulin release and insulin resistance.     

Effects of feeding state on glycaemic and insulinaemic responses to a starchy meal in horses: a methodological approach

A standardised methodology is required for classification of starchy diets. One important question is what feeding status is optimal to describe glycaemic and insulinaemic responses to the respective starchy diet. Four horses were fed, in a randomised order, four different feeding protocols relative to offering hay before or after cracked corn (CC): (i) ad libitum hay for 12 h before feeding CC and ad libitum hay after CC intake for 9 h (+CC+), (ii) ad libitum hay for 12 h before feeding CC and no hay after CC intake for 9 h (+CC-), (iii) feed restriction for 12 h before feeding CC and ad libitum hay after CC intake for 9 h (-CC+) and (iv) 1.2 kg hay/100 kg body weight (BW) per day, divided into two equal portions and offered at 0900 h and 1900 h, feed restriction for 12 h before feeding CC and no hay after CC intake for 9 h (-CC-). CC intake was adjusted to a starch intake of 2 g/kg BW. The different hay offerings did not affect basal plasma glucose and insulin levels. A significant rise in plasma glucose and insulin was found after CC intake for all diets. The highest peak glucose levels were analysed for -CC+, and the lowest glucose peaks were found for +CC- (diet P < 0.05). The highest insulin peaks were monitored for -CC+ (31.27 ± 18.19 μU/ml) and lower peaks for +CC- (13.36 ± 2.93 μU/ml) (diet P < 0.05). Insulin for -CC- and +CC- returned to resting values about 300 min after CC feeding. For +CC+ and -CC+, insulin levels were still above resting levels 510 min after CC intake (diet P < 0.05). The present data suggest that feed restriction for 12 h before feeding the starchy diet and no further roughage intake during blood sampling period provide the best-defined conditions.     

Changes of plasma insulin, urea, amino acids and rumen metabolites in somatotropin treated dairy cows

Summary An experiment was performed to evaluate the effects of somatotropin on plasma free amino acid, urea and insulin concentrations and rumen fermentation pattern and to assess their relationships. Four Italian Friesian dairy cows fitted with rumen cannulae were used in a switch-back design. Slow releasing recombinant bovine somatotropin (640 mg/cow) was injected every 28 days for two consecutive periods. Rumen fluid and blood samples were collected before and after feeding at 0, 7 and 21 days after rbST injection. Exogenous rbST increased plasma insulin concentration and the insulin response to feeding, and decreased plasma urea and free essential and branched chain amino acid concentrations. rbST did not affect rumen fermentation pattern. No correlation was found between rumen and plasma parameters measured after feeding. Our results are consistent with the notion that the main effect of somatotropin is post-absorptive.     

The effects of continuous infusions of prostacyclin-Na (epoprostenol-sodium) on platelet counts, ADP-induced aggregation, and cyclic AMP levels in normal volunteers

Six male volunteers received either 0 (buffer), 2.5 or 5.0 ng/kg/min PGI2 X Na for 72 hrs. Various platelet parameters were monitored for an additional 72 hrs. Each morning, for seven consecutive days, and +1 and +6 hrs after the termination of the infusion, blood was drawn and platelet rich plasma (PRP) was prepared. The PRP was immediately exposed to 100 ng/ml PGI2 X Na, and the subsequent increase in platelet cyclic AMP was measured by radioimmunoassay. Aggregation in response to 2 or 4 microM ADP was measured simultaneously. Three volunteers returned for a second 72 hr infusion of 5.0 ng/kg/min PGI2 X Na. After 72 hrs, the infusion rate was gradually "tapered off" over a 12 hr period at which time the infusion was terminated. The sensitivity of the PRP to ADP-induced aggregation was recorded before, during, and after the "tapering off" regimen. Platelet counts were not altered by any of the infusions. The responsiveness of the platelet adenylate cyclase to exogenous PGI2 X Na was inversely related to the concentration of PGI2 X Na infused. Desensitization occurred and was more severe after 72 hrs of infusion than after either 24 or 48 hrs. For example, after 72 hrs at 5.0 ng/kg, platelets lost approximately 50% of their responsiveness to PGI2. ADP-induced aggregation was not significantly inhibited ex vivo by the infusion of 2.5 ng/kg/min PGI2. During the infusion of 5.0 ng/kg/min PGI2, ADP-induced aggregation was inhibited at 24 and 48 hrs, but by 72 hrs, the platelets began to respond to ADP more like control cells even though the PGI2 X Na infusion was continuing. When the infusion was abruptly terminated a hyperaggregable response (rebound) to exogenous ADP was observed. In subjects where the 5.0 ng/kg/min infusion was gradually "tapered off" over a 12 hr period, there was no evidence of platelet hyperaggregability at the time points studied.     

Somatostatin-induced inhibition of insulin secretion from isolated islets of rat pancreas in presence of glucagon.

In order to study the oeffect of somatostatin on the endocrine pancreas directly, islets isolated from rat pancreas by collagenase were incubated for 2 hrs 1) at 50 and 200 mg/100 ml glucose in the absence and presence of somatostatin (1, 10 and 100 mg/ml) and2) at 200 mg/100 ml glucose together with glucagon (5 mug/ml), with or without somatostatin (100 ng/ml). Immunologically measurable insulin was determined in the incubation media at 0, 1 and 2 hrs. Insulin release was not statistically affected by any concentration stomatostatin. On the other hand, somatostatin exerted a significant inhibitory action on glucagon-potentiated insulin secretion (mean +/- SEM, mu1/2 hrs/10 islets: glucose and glucagon: 1253 +/- 92; glucose, glucagon and somatostatin: 786 +/- 76). The insulin output in th epresence of glucose, glucagon and somatostatin was also significantly smaller than in thepresence of glucose alone (1104 +/- 126) or of glucose and somatostatin (1061 +/- 122). The failure of somatostatin to affect glucose-stimulated release of insulin from isolated islets contrasts its inhibitory action on insulin secretion as observed in the isolated perfused pancreas and in vivo. This discrepancy might be ascribed to the isolation procedure using collagenase. However, somatostatin inhibited glucagon-potentiated insulin secretion in isolated islets which resulted in even lower insulin levels than obtained in the parallel experiments without glucagon. It is concluded that the hormone of the alpha cells, or the cyclic AMP system, might play a part in the machanism of somatostatin-induced inhibition of insulin release from the beta-cell.     

Human ultralente insulin.

The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). There was no significant difference between human and bovine insulin in the rise in plasma glucose concentration from 0400 to 0700 after an injection the previous morning and no difference between patients receiving an adequate or insufficient dose of human ultralente insulin. Bovine insulin antibody binding was reduced with human insulin (p less than 0.002), which suggests that human insulin is less antigenic than beef insulin. Once daily human ultralente insulin provides a suitable formulation for the basal insulin requirement of diabetics.     

Salt and the glycaemic response.

The possibility that salt increases plasma glucose and insulin responses to starchy foods was investigated. Six healthy adults took four morning test meals randomly: 50 g carbohydrate as cooked lentils or white bread, with or without 4.25 g of added salt (an amount within the range of salt found in a meal). When salt was added to the lentils the incremental area under the three hour plasma glucose curve was significantly greater than that for lentils alone (43.2 mmol.min/l v 11.1 mmol.min/l (778 mg.min/100 ml v 200 mg.min/100 ml]. When salt was added to bread the peak glucose concentration was significantly higher than that for unsalted bread (6.96 mmol/l v 6.35 mmol/l (125 mg/100 ml v 114 mg/100 ml], and this was followed by relative hypoglycaemia. Plasma insulin concentrations at 45 minutes were higher after a meal of salted lentils and salted bread than after the unsalted foods (p less than 0.05). The high insulin concentration after salted bread was sustained for one hour after the meal, thus the mean area under the three hour curve was 39% greater than that for unsalted bread (p less than 0.05). Salt may increase the postprandial plasma glucose and insulin responses to lentils and bread by accelerating the digestion of starch by stimulating amylase activity or accelerating small intestinal absorption of the liberated glucose, or both. The findings of this preliminary study, if confirmed by others, would support the recommendation that diabetics, as well as the general population, should reduce their intake of salt.     

Exogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion during Acute Sepsis in Non-Diabetic Mice

Objectives

The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT). We next extended our findings using a cecal ligation and puncture (CLP) sepsis model administered early parenteral glucose support.

Methods

Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg) in the presence of saline or glucose infusion (100 µL/hr), and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs.

Measurements

And MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl) associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL) or sham mice receiving parenteral glucose (113 ± 3 mg/dL) all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml) was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml).

Conclusions

The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin secretion, leading to the development of fulminant hyperglycemia.     

Effects of psychoactive and non-psychoactive cannabinoids on neuroendocrine and testicular responsiveness in mice

Repeated oral administration of the non-psychoactive cannabinol (CBN; 5 or 50 mg/kg) significantly reduced the concentration of norepinephrine (NE) in median eminence and greatly reduced NE levels 1 and 2 hrs after administration of alpha-methylparatyrosine (alpha-MPT). The levels of dopamine (DA) in median eminence were significantly different, as indicated by the differences in slopes obtained in CBN- treated and control mice before and after alpha-MPT. Plasma levels of luteinizing hormone (LH) were significantly reduced in CBN-exposed mice before alpha-MPT, elevated at 1 hr post-injection, but were also reduced 2 hrs post-injection at 50 mg/kg CBN. Follicle-stimulating hormone (FSH) levels were increased at 1 hr post-alpha-MPT in mice receiving 50 mg/kg CBN. Oral administration of CBN at 50 mg/kg for 4 days enhanced testicular testosterone (T) production in response to intratesticular in vivo injection of 2.5 or 25 mIU human chorionic gonadotropin (hCG). A single oral dose of the psychoactive delta 9-tetrahydrocannabinol (THC) enhanced the production of T 15 min after intratesticular LH (10 ng) injection. However, at 45 or 60 min post-THC treatment, the response to LH was significantly attenuated. These studies demonstrate that both psychoactive and non-psychoactive components of marihuana alter testicular responsiveness to gonadotropins in vivo. These effects may be biphasic, involving stimulation and inhibition of responsiveness, and appear to be correlated with alterations in plasma LH levels. Alterations in plasma gonadotropins may be mediated by cannabinoid effects on catecholamine concentrations in median eminence and THC-induced alterations in testicular responsiveness to gonadotropin probably also involve direct effects of THC at the gonadal level.     

Bile salts promote the absorption of insulin from the rat colon

The absorption of insulin mixed with sodium deoxycholate (DOC) or sodium cholate from the rectal mucosa of diabetic and non-diabetic rats was measured by the effect on blood glucose levels. Blood sugar was lowere by 50% one hour after administration of 12 u soluble insulin mixed with 1–10 mg/ml DOC, or 2–20 mg/ml sodium cholate. There was a linear correlation between the reduction in blood glucose and the amount of insulin administered (1–64 units) when mixed with 5 mg/ml DOC. Radioimmuno-assay of plasma insulin showed an increase from 16.2 μu/ml to 3335 muuu/ml after rectal administration of 12 u soluble insulin. We conclude that insulin when mixed with bile salts can be absorbed by the intestine to reach the circulation in a biologically active form.     

Response of the hypothalamo-corticotropic system to metyrapone in pigeons

Chronic catheterization and miniature recording device allowed plasma corticosterone (B) and hypothalamic multiunit activity (MUA) to be simultaneously obtained from freely behaving, awake pigeons, before and for 4 hrs after intravenous injection of metyrapone. Injection of vehicle (tartric acid : 100 mg/4 ml/kg) led to MUA and B profiles quite similar to stress-induced responses, i.e., a rapid and sustained rebounding increase in hypothalamic firing rate and, shifted by 5-10 min, in plasma B. These responses were progressively attenuating for 90-120 mn. Metyrapone administration induced first a rapid and short MUA and B increase. Then both parameters drastically decreased near zero for about 2 hrs and were slowly restored to initial values within 3-4 hrs. It is suggested that metyrapone treatment inhibited both peripheral (B synthesis) and central (hypothalamic neurons) levels of the corticotropic axis.     

Prostaglandin Release at Dexamethasone Induced Parturitions in Cows

Three cows of the Swedish Red and White Breed (SRB) were used in the experiment. Cow no. 1 pregnant for 247 days, was given 20 mg dexamethasone twice with an interval of 48 hrs. Cows nos. 2 and 3, each pregnant for 254 days, received 20 mg of dexamethasone twice with an interval of 24 hrs. The cows delivered normal living calves 153, 138 and 137 hrs., respectively, after the second injection of dexamethasone. Blood samples were drawn from the jugular vein every third hour during the experimental period and the samples were analyzed for estrone, progesterone and 15-keto-13,14-dihydroprostaglandin F2α. Following the dexamethasone injections there was a continuous increase in the blood plasma levels of estrone followed by a sharp decrease in conjunction with parturition. The blood plasma level of progesterone showed a slow but continuous decrease until about 24 hrs. before delivery when a marked drop occurred. The levels of the prostaglandin metabolite increased gradually until about 24 hrs. prior to delivery. This was followed by an abrupt rise, and high levels of the prostaglandin metabolite were recorded for up to four days following parturition. It is concluded that the estrone increase preceded that of the prostaglandin metabolite and that the final drop in the progesterone was synchronous with the final rise of the prostaglandin metabolite level.     

Effect of bromocriptine on lipid plasma levels in rats

Results show that bromocriptine induced marked alterations in plasma levels of cholesterol and lipids in response to acute and chronic administrations in rats. Two hours after an I.P. dose of 10 mg/kg, bromocriptine mesylate caused significant reductions in plasma levels of total high density lipoprotein (HDL) and high density lipoprotein cholesterol (HDL cholesterol). At a dose of 20 mg/kg, bromocriptine mesylate induced significant elevations in plasma levels of total cholesterol, total HDL, HDL cholesterol, total low density lipoproteins (LDL), and low density lipoprotein cholesterol (LDL cholesterol). Injected at a dose of 4 or 10 mg/kg daily for 14 consecutive days, bromocriptine mesylate caused significant increases in plasma levels of total cholesterol, LDL cholesterol and total LDL whereas the levels of HDL cholesterol, total HDL triglycerides (TG) were reduced. At a dose of 20 mg/kg all parameters were significantly increased. Marked hyperglycaemia was noticed in response to doses of 10, 15 and 20 mg/kg injected daily for 14 consecutive days or 2 hrs after a single administration of 15 mg/kg. Plasma insulin activity was reduced 2 hours after injection of bromocriptine at a dose of 15 mg/kg Likewise, a significant reduction in plasma insulin activity was observed in response to daily I.P. injections of bromocriptine at a dose of 15 mg/kg. Hyperglycaemic and hypoinsulinaemic effects of bromocriptine (acute and chronic) were markedly decreased when sulpiride, a dopaminergic D2 antagonist, was injected at an I.P. dose of 10 mg/kg before bromocriptine. Plasma ACTH activity was significantly increased in response to bromocriptine (15 mg/kg I.P.) in acute and chronic experiments. This effect was markedly diminished when sulpiride was injected prior to bromocriptine. In conclusion, bromocriptine induced marked elevations in plasma levels of total cholesterol and lipids which are likely to be related to hyperglycaemic and hypoinsulinaemic effects.     

Steroid levels after intramuscular injection of radioactive estradiol-17beta, estrone, progesterone and testosterone in the bovine

Eight 2 year old Hereford cows from days 8 to 12 of the estrous cycle were injected intramuscularly with 5 ml of corn oil containing 5 mg of estradiol-17beta (two cows), estrone (two cows), progesterone (two cows) or testosterone (two cows). Each cow treated with estradiol received 494 microc of estradiol-17beta-6, 7 H3 and each cow treated with estrone received 492 microc of estrone-6, 7 H3. Each cow treated with progesterone or testosterone received 400 muc of H3 compound labeled in the 7 position. Total urine was collected by urethral catheterization of the cows treated with estrogens. Blood samples for plasma and serum were collected via jugular cannulae. Blood and urine samples from estrogen-treated cows were collected hourly for the first 24 hr, at 2 hr intervals for the next 26 hr, at 4 hr intervals for the next 12 hr and at 12 hr intervals until background was reached. Blood samples were collected hourly from 1 to 8 hr after injection from progesterone or testosterone-treated cows. Plasma and serum levels of radioactive estradiol-17beta, estrone, progesterone and testosterone were similar. Blood levels of radioactivity peaked at 2 hr post-injection in cows receiving estradiol-17beta and at 3 hr in cows receiving estrone. Blood levels of labeled estradiol-17beta and estrone were nondetectable by 54 hr and 83 hr, respectively. Peak urinary excretion of radioactivity was reached at 7 hr for estradiol-17beta and at 14 hr for estrone and nondetectable levels were reached by 95 hr for estradiol-17beta and 14 hr for estrone. At these times, 15.5% of the total dose of radioactive estradiol-17beta and 17.5% of the injected estrone had been excreted in the urine. Peak blood and urinary excretion levels were reached earlier for radioactive estradiol-17beta than for estrone, and excretion of estradiol-17beta was completed more rapidly. No difference was found in plasma and serum levels for any steroid studies; thus, endogenous steroid titers in blood plasma and serum are not different in the cow.     

Evidence of an insulin generated pyruvate dehydrogenase stimulating factor in rat brain plasma membranes

1. The results of this study indicates that the binding of insulin to brain plasma membranes activates a membrane protease which, by a trypsin like mechanism, produces a soluble factor that modulates the PDH behaviour when added to brain mitochondria. 2. The supernatant from brain plasma membranes incubated with 0.5 mg/ml trypsin added to mitochondria increases PDH activity levels and cancels PDH inhibition by NaF, as has already been seen when the plasma membranes are incubated with 25 microU/ml insulin. No such effects are obtained when the incubation is run out with 0.5 mg/ml chymotrypsin. 3. The supernatants from insulin or trypsin treated plasma membranes retain their activating properties on mitochondrial PDH also after dansylation; from these preparations a dansylated active on PDH material was separated by monodimensional chromatography on HPTLC silica Gel plates, using chloroform/1-butanol (93:7 v/v) as a solvent. 4. Insulin incubation of plasma membranes pretreated with protease inhibitors (leupeptin, phenylmethylsulfonylfluoride) or with exogenous trypsin, but not chymotrypsin substrates (esters of arginine and tyrosine) yields an inactive supernatant on PDH. 5. Insulin treated plasma membrane supernatants lose all stimulating properties on PDH after incubation for 1 hr with 2 mg/ml trypsin or chymotrypsin.     

Insulin secretion and glucose uptake in hypomagnesemic sheep fed a low magnesium, high potassium diet

Hyperglycemic and euglycemic clamp experiments were conducted to evaluate insulin secretion and glucose uptake in the hypomagnesemic sheep fed a low magnesium (Mg), high potassium (K) diet. Five mature sheep were fed a semipurified diet containing 0.24% Mg and 0.56% K (control diet) and five were fed 0.04% Mg and 3.78% K (low Mg/high K diet) for at least 2 weeks. In the hyperglycemic clamp experiment, plasma glucose concentrations were raised and maintained at a hyperglycemic steady-state (approximately 130 mg/100 ml) by variable rates of glucose infusion during the experimental period (120 minutes). The insulin response in the sheep fed the low Mg/high K diet (31.0 microU/ml) were significantly (P < 0.01) lower than those (111.7 microU/ml) of the sheep fed the control diet. In the euglycemic clamp experiment, insulin was infused at rates of 5, 10, 15, or 20 mU/kg/min, each followed by variable rates of glucose infusion to maintain a euglycemic steady-state (basal fasting levels). Hypomagnesemic sheep fed the low Mg/high K diet had significantly (P < 0.01) lower mean glucose disposal (3.72 mg/kg/min) across the insulin infusion rates compared with those of the sheep fed the control diet (5.37 mg/kg/min). These results suggest that glucose-induced insulin secretion and insulin-induced glucose uptake would be depressed in hypomagnesemic sheep and are caused by feeding the low Mg/high K diet.