Differences In Plasma Insulin Concentrations Research Articles

Effects of encapsulated niacin on metabolism and production of periparturient dairy cows

Nicotinic acid (niacin) can suppress lipolysis, but responses to dietary niacin have been inconsistent in cattle. Our aim was to determine if 24g/d of encapsulated niacin (EN; providing 9.6g/d of bioavailable nicotinic acid) alters lipid metabolism and productivity of transition cows. Beginning 21 d before expected calving, primiparous (n=9) and multiparous (n=13) cows (body condition score of 3.63±0.08) were sequentially assigned within parity to EN (12g provided with ration twice daily) or control through 21 d postpartum. Liver biopsies were collected on d −21, −4, 1, 7, and 21 relative to parturition. Blood samples were collected on d −21, −14, −7, −4, 1, 4, 7, 14, and 21 relative to parturition. On d 7 postpartum, a caffeine clearance test was performed to assess liver function, and on d 21 to 23 postpartum, blood samples were collected every 8h to monitor posttreatment nonesterified fatty acid (NEFA) responses. Data were analyzed using mixed models with repeated measures over time. A treatment × time × parity effect was observed on prepartum dry matter intake (DMI), which was caused by a 4kg/d decrease in DMI of EN-treated multiparous cows compared with control multiparous cows during the final 4 d prepartum. A significant increase in plasma nicotinamide concentration occurred in EN-treated cows on d −7 and 21 relative to parturition. Prepartum glucose concentration decreased in treated animals, with no difference in plasma insulin concentration. Treatment × time × parity effects were detected for NEFA and β-hydroxybutyrate concentrations during the postpartum period. Plasma NEFA peaked at 1,467±160μM for control animals compared with 835±154μM for EN-treated animals. After treatments ended on d 21, no evidence was found for a plasma NEFA rebound in either parity group. A treatment × parity × time interaction was detected for liver triglyceride content, indicating a tendency for less liver triglyceride in EN-treated primiparous cows, but caffeine clearance rates were not affected by treatment. No treatment effects were observed for body condition score, body weight, energy balance, or milk or milk component production. A high dose of EN can decrease postpartum plasma NEFA concentration, but may also decrease prepartum DMI.

Differences in the pharmacokinetics of Cyp3a substrates in TSOD and streptozotocin-induced diabetic mice

The pharmacokinetics of drugs can change in diabetes mellitus and even among diabetics. They may differ between type I diabetes (T1DM) and type 2 diabetes (T2DM).As triazolam was administered orally to Tsumura, Suzuki, obese, diabetes (TSOD) mice and streptozotocin (STZ) mice, clearance per body (CL/F) in TSOD mice did not differ compared with Tsumura, Suzuki, non-obesity (TSNO) mice. In STZ mice, CL/F was greater than in control mice. Small intestinal cytochrome P450 (Cyp) 3a expression in TSOD mice was significantly lower than in TSNO mice. No significant difference existed in small intestinal Cyp3a expression between STZ mice and control mice. In insulin-treated mice, small intestinal Cyp3a expression was significantly lower than in control mice.These results suggested that the differences in changes in small intestinal Cyp3a expression between T1DM and T2DM may be due to differences in plasma insulin concentrations. This may be a factor in the difference in the drug pharmacokinetics between T2DM and T1DM patients.

Abstract 5038: Enhanced Endothelial-specific Insulin Sensitivity Regulates Whole Body Glucose Homeostasis and Endothelial Function

Accumulating evidence now suggests that insulin resistance may promote atherosclerosis through a closely coupled association with endothelial dysfunction, and that the relationship between insulin resistance and endothelial function is reciprocal. However the role of the endothelium in whole body glucose regulation until now has remained unclear. SHIP2 is a lipid phosphatase which acts as a negative regulator of insulin signalling. In this study Cre-Lox technology is used to generate an endothelial-specific SHIP2 haploinsuffient mouse, as a model of enhanced endothelial-specific insulin sensitivity. We have investigated both the metabolic and vascular phenotype of this model to determine whether enhanced insulin signalling in endothelium modulates vascular function and whole body glucose regulation. Results described are from male EC-SHIP2 +/− offspring compared with control sex-matched littermates at 12–16 weeks of age. EC-SHIP +/− mice were morphologically indistinguishable from control littermates, exhibited normal development and body and organ masses were similar in both groups. No significant differences were observed in heart rate or blood pressure. Glucose tolerance after glucose challenge was found to be significantly better in EC-SHIP +/− than controls (p = <0.05), with no differences in plasma insulin concentrations; fasted or after glucose challenge. Improved insulin sensitivity was confirmed in EC-SHIP +/− mice in insulin tolerance tests (p = <0.05). e x vivo vasomotor studies in aorta revealed no significant differences between EC-SHIP +/− and controls in contractile responses to phenylephrine or maximal relaxation to sodium nitroprusside and ACh. However, basal phosphorylation of eNOS (Ser-1177) was greater in EC-SHIP +/− aorta than controls. In conclusion; the results suggest endothelial partial deletion of SHIP2 confers important effects on metabolic homeostasis and endothelial function. In particular, improved glucose tolerance and insulin sensitivity in EC-SHIP +/− mice support a critical role for insulin signalling in endothelial cells in whole body glucose regulation.

Is There Peripheral or Ovarian Insulin Action Alteration in Broiler Breeder Hens Fed ad Libitum?

We investigated whether a change in peripheral glucose homeostasis, a local change in the insulin- related ovarian regulatory system, or both occurred in ad libitum-fed broiler breeder hens compared with feed-restricted counterparts. Feed-restricted (R, from 5 to 16 wk of age) and ad libitum-fed (A) hens from a standard commercial line (S) and an experimental dwarf genotype (E) were studied. Basal and stimulated plasma insulin and glucose concentrations were measured during the prebreeding and laying periods. In the basal state (after 16 h fasting) plasma glucose concentrations were significantly lower in SA chickens (-5% at 17 wk, -7.5% at 32 wk) compared with EA, SR, and ER chickens, with no difference in plasma insulin concentrations (n = 16). In 17-wk-old SA birds, 30 min after oral glucose loading, plasma glucose concentrations increased significantlycompared with the basal state and were also significantly lower as compared with SR but did not differ significantly from EA and ER. Plasma insulin concentrations did not differ significantly between genotypes or regimens (n = 16). A potential modification of intracellular mediators involved in the regulation of cell growth and survival in small follicles that were overrecruited in SA compared with SR was also investigated in SA and SR hens at 32 wk. There was no effect of food restriction in phospho- Akt, Akt, phospho-ERK, and phospho-S6 in the small white ovarian follicles (n = 6) in the basal state and after 30 min of refeeding. In conclusion, the present study does not demonstrate any evidence of glucose intolerance during the prebreeding period, specific change in the ovarian small follicle insulin signalling pathway, or both, in laying broiler breeders fed ad libitum compared with feed-restricted hens.

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

Nitric oxide (NO) has been implicated as an important signalling molecule in the contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control. The current study sought to determine whether acute infusion of the NO donor, sodium nitroprusside (SNP), increases leg glucose uptake at rest in patients with type 2 diabetes. Fifteen male patients with type 2 diabetes (aged 54+/-4 years, mean+/-SD) were entered into a randomised, cross-over design study, examining the effect of a 30-min intra-femoral infusion of SNP on leg glucose uptake. Comparison was made with a 30-min infusion of verapamil, titrated to elicit similar leg blood flow responses to SNP. Leg blood flow was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of leg blood flow and the femoral arterio-venous (A-V) glucose concentration gradient. The two drugs increased leg blood flow to a similar extent (p=0.50). Both leg A-V glucose concentration gradient (SNP 0.12+/-0.05, verapamil -0.06+/-0.04 mmol/l; mean+/- SEM, p=0.03) and leg glucose uptake (SNP 0.17+/-0.09, verapamil -0.09+/-0.06 mmol/min; p=0.03) were higher with the SNP treatment than with verapamil. These results occurred independently of any significant difference in plasma insulin concentration between drugs (p=0.56). Acute infusion of SNP resulted in greater glucose uptake relative to verapamil. NO may therefore be an important mediator of peripheral glucose disposal and a potential therapeutic target in patients with type 2 diabetes.

Effect of dietary-induced increases in circulating insulin concentrations during the early postpartum period on reproductive function in dairy cows

Although it has become increasingly clear that fertility in modern dairy cattle is declining in association with increased milk yields, the underlying mechanism is poorly understood. The first ovulation post partum is delayed in dairy cows undergoing selection for genetic merit for milk yield in association with lower circulating insulin concentrations. The aim of this study was to investigate whether feeding a diet to increase circulating insulin concentrations can overcome this delay in the first ovulation post partum. The experiment was a 2 x 2 factorial design (n = 10 per group) involving diet and genetic merit for milk yield. The dietary treatment started on the day of calving and lasted for 50 days. Plasma samples were collected each day and ovarian ultra-sonography was performed three times a week during the experimental feeding period. Milk yield was recorded each day, and body weight and body condition score were determined each week. Milk samples were collected three times a week from day 50 to day 105 post partum, and reproductive performance data were recorded for all the cows as part of the routine farm practice. The dietary treatment induced significant differences in plasma insulin concentrations in both high and low genetic merit cows. Although high genetic merit cows produced more milk, lost more body weight and had lower body condition scores during the experiment, no significant effect of diet was observed on these measurements. The high insulin inducing diet increased the proportion of cows ovulating within 50 days of calving and reduced the intervals from calving to first ovulation, and tended to reduce the intervals from calving to first service and to conception. These fertility parameters were also more favourable in low than in high genetic merit cows, but no interaction between diet and genetic merit was observed for any of these parameters. Genetic merit, but not diet, also affected the number of services required per conception and the conception rate. In conclusion, these results have confirmed that genetic selection for high milk yield is associated with a decrease in reproductive performance in dairy cows. More importantly, this study has demonstrated that it is possible to alleviate this problem by nutritional manipulation.

Effect of dietary-induced increases in circulating insulin concentrations during the early postpartum period on reproductive function in dairy cows

Although it has become increasingly clear that fertility in modern dairy cattle is declining in association with increased milk yields, the underlying mechanism is poorly understood. The first ovulation post partum is delayed in dairy cows undergoing selection for genetic merit for milk yield in association with lower circulating insulin concentrations. The aim of this study was to investigate whether feeding a diet to increase circulating insulin concentrations can overcome this delay in the first ovulation post partum. The experiment was a 2 x 2 factorial design (n = 10 per group) involving diet and genetic merit for milk yield. The dietary treatment started on the day of calving and lasted for 50 days. Plasma samples were collected each day and ovarian ultra-sonography was performed three times a week during the experimental feeding period. Milk yield was recorded each day, and body weight and body condition score were determined each week. Milk samples were collected three times a week from day 50 to day 105 post partum, and reproductive performance data were recorded for all the cows as part of the routine farm practice. The dietary treatment induced significant differences in plasma insulin concentrations in both high and low genetic merit cows. Although high genetic merit cows produced more milk, lost more body weight and had lower body condition scores during the experiment, no significant effect of diet was observed on these measurements. The high insulin inducing diet increased the proportion of cows ovulating within 50 days of calving and reduced the intervals from calving to first ovulation, and tended to reduce the intervals from calving to first service and to conception. These fertility parameters were also more favourable in low than in high genetic merit cows, but no interaction between diet and genetic merit was observed for any of these parameters. Genetic merit, but not diet, also affected the number of services required per conception and the conception rate. In conclusion, these results have confirmed that genetic selection for high milk yield is associated with a decrease in reproductive performance in dairy cows. More importantly, this study has demonstrated that it is possible to alleviate this problem by nutritional manipulation.

Birth weight responses to shearing ewes in early to mid gestation

AbstractThis study compared the effect on foetal growth of shearing ewes in very early pregnancy (day 50) with the effect of shearing later in pregnancy (day 70 or 100). One hundred and sixty ewes were allocated at day 49 of pregnancy to four ‘time of shearing’ treatments — pregnancy day 50 (P50), P70, P100 (no. = 45 ewes per treatment) and unshorn (shearing of this group occurred 43 days after weaning) (no. = 25); two methods of shearing (by standard comb and cover comb); and two levels (1 or 2) of pregnancy/rearing rank. All ewes had been mated over a 28-day period and grazed pasture throughout the trial. The mid point of lambing was 27 August 1996. Live weights of ewes (corrected for fleece weight) were not influenced by shearing time at any stage except at day 45 of lactation when ewes shorn at P50, P70 or P100 were about 3⋅0 kg lighter than unshorn ewes. Shearing method had no effect on ewe live weight. Time of shearing and shearing method had no effect on ewe greasy fleece production or wool tensile strength. Shearing significantly (P < 0⋅05) influenced the birth weight of single- (by 0⋅7 to 0⋅8 kg) but not twin-born lambs. Maternal plasma triiodothyronine concentration increased proportionately by 0⋅47 to 0⋅85 (P < 0⋅05) and lasted for at least 20 days in response to shearing irrespective of time of shearing. No difference in plasma insulin concentration was detected between shearing groups but plasma glucose concentration proportionately increased by 0⋅06 to 0⋅16 (P < 0⋅05) for 10 to 20 days after shearing. These results indicate that shearing between day 50 and 100 of pregnancy can increase lamb birth weights and that the response is associated with an increase in thyroid hormone concentrations in the maternal circulation.

Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue.

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the s.c. adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

Effect of ketone bodies on hyperglycemia and lactic acidemia in hemorrhagic stress.

To investigate the effect of hyperketonemia on altered glucose metabolism under stress conditions, we infused sodium D-3-hydroxybutyrate (3-OHB) into rats in hemorrhagic hypotension and evaluated the plasma concentration of substrates related to glucose metabolism. Three groups of anesthetized rats (weight, 280 g to 320 g) were bled acutely, and their mean arterial pressures were maintained at 40 mm Hg. From 1 hour before hemorrhage to the end of the experiment, rats in the first group (n = 10) were infused with 3-OHB at a rate of 30 mumol/kg.min (3-OHB group), those in the second group (n = 10) received glucose and sodium bicarbonate (glucose group), and the remaining 10 rats received only sodium bicarbonate and no energy substrates (control group). Sodium bicarbonate was used to control the alkalizing effect of 3-OHB. Hyperketonemia (1158 +/- 30 mumol/L - 1618 +/- 154 mumol/L) occurred only in the 3-OHB group. Hyperglycemia and lactic acidemia during hemorrhagic shock were suppressed significantly compared with the control group. Plasma concentration of alanine was also lower compared with the control group. In the glucose group, although plasma lactate concentration was lower, plasma glucose concentration was not suppressed, and plasma alanine concentration was higher in comparison with the control group during hemorrhagic shock. There was no significant difference in plasma insulin concentration among the three groups. These results suggest that administered 3-OHB may suppress glycolysis during hemorrhagic shock.

Benfluorex decreases insulin resistance and improves lipid profiles in obese type 2 diabetic patients

Benfluorex hydrochloride has known lipid- and glucose-lowering effects. We evaluated the change in lipids, fasting glucose, and insulin sensitivity in ten obese type 2 diabetic patients after treatment with benfluorex or a placebo for 2 weeks using a double-blind, cross-over design. Insulin sensitivity was measured using the euglycaemic-hyperinsulinaemic glucose clamp technique at two insulin infusion rates for 2 h each: 0.05 U/kg per h (clamp 1) and 0.10 U/kg per h (clamp 2). Mean fasting glucose decreased from 13.1 +/- 1.1 to 10.2 +/- 0.9 mmol/l after benfluorex (p < 0.001) and rose from 11.9 +/- 0.9 to 13.3 +/- 1.0 mmol/l after the placebo (p = 0.028). Insulin did not change significantly. Glucose uptake (GU) as a parameter for insulin sensitivity was compared for treatment with benfluorex versus the placebo. Total GU during clamp 1 was 643.4 +/- 323.8 mmol after benfluorex and 250.1 +/- 193.3 mmol after the placebo (p = 0.035), and during clamp 2, 2490.7 +/- 490.5 mmol after benfluorex and 1544.3 +/- 693.9 mmol after the placebo (p = 0.018). The dynamic analysis on the last 30 min of clamp 2 showed a significant difference in glucose infusion rate (GIR) profile, with mean levels yielding 5.36 mmol/kg per min after benfluorex and 3.87 mmol/kg per min after the placebo (p = 0.018); there were no differences in plasma insulin concentrations or plasma glucose levels. It is concluded that in this short-term study benfluorex increases insulin sensitivity in obese type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic characteristics of hypertension: Importance of positive family history

This study was performed to compare metabolic and endocrine characteristics of untreated hypertensive patients and normal controls. Measurements were made in age-matched, body mass index (BMI) matched, normotensive patients with ( n = 40; age = 53; BMI = 28) and without ( n = 39; age = 54; BMI = 27) a family history of hypertension and hypertensive patients with ( n = 38; age = 53; BMI = 28) and without ( n = 25; age = 54; BMI = 29) a family history of hypertension. Norepinephrine, renin activity, and total cholesterol blood concentrations were similar in normotensive patients with a positive family history of hypertension and in hypertensive patients with or without a family history. Similarly, there were no differences in plasma insulin concentrations or insulin/glucose ratios between the normotensive patients with a family history of hypertension and hypertensive patients with or without a family history. But in all three groups the values were significantly greater (at least p < 0.05 for each) than in the normotensive patients without a family history. Increases in systolic blood pressure during treadmill testing were 51 ± 4 mm Hg in the normotensive patients with a family history, 50 ± 3 mm Hg in hypertensives with a family history, and 45 ± 5 mm Hg in hypertensives without a family history; these changes were all less ( p < 0.05 for each) than in normotensives without a family history (65 ± 3 mm Hg). Together, these findings indicate that patients with a family history of hypertension, regardless of whether their own blood pressures are normal or high, exhibit clinical characteristics that may be predictive of an increased risk of cardiovascular events.

Increased insulin suppression of plasma free fatty acid concentration in exercise-trained rats.

The effect of exercise training on the insulin suppression of plasma free fatty acid (FFA) concentrations was studied in unanesthetized rats with the hyperinsulinemic-euglycemic clamp technique. Seven rats trained (TR) for 3 h/day by continuous swimming during 8 wk were compared with 6 untrained (UT) body weight-matched rats. Both TR and UT rats were submitted to an exercise swimming session 18 h before the clamp. A smaller mean diameter of adipocytes sampled from the epididymal fat depot was measured in TR animals. The total quantity of glucose infused to maintain euglycemia was 2.2 times higher in TR than in UT animals. No significant differences in plasma insulin concentrations were found between the two groups throughout the experiment. Insulin infusions resulted in a 60% decrease of plasma FFA in TR rats (mean value: from 0.46 to 0.18 mM) compared with 27% in UT animals (mean value: from 0.45 to 0.33 mM). The data indicate a greater ability of insulin to suppress plasma FFA levels with exercise training, which suggests an increased antilipolytic action of insulin in adipocytes under this condition.

Early metabolic effects of sepsis in the preterm infant: Lactic acidosis and increased glucose requirement

The effects of sepsis on carbohydrate metabolism were studied in preterm newborn infants (weight > 1.2 kg, appropriate for gestational age) without maternal endocrine problems who were being examined for infection. Plasma glucose, lactate, and insulin concentrations were measured at initial evaluation and then every 8 hours for a total of 48 hours. Blood, urine, and spinal fluid were obtained for culture and counterimmunoelectrophoresis. Dextrose was administered to each patient to maintain glucose levels in the normal range. Dextrose infusion rates were calculated in milligrams per kilogram per minute. Of the 29 infants, 6 had sepsis (positive culture and counterimmunoelectrophoresis results). Infants with sepsis had significant elevations of plasma lactate concentration (p < 0.003) but normal pH. The dextrose infusion rate was also significantly elevated in the infected infants (p < 0.01). No hypoglycemia or hyperglycemia was observed in either group. No significant difference in plasma insulin concentration was observed. We conclude that significant elevations in plasma lactate concentrations and dextrose infusion rate may be early clinical markers of neonatal sepsis in the first 48 hours of life.

The effect of energy source and feeding level on the hormones of the entero-insular axis and plasma glucose in the growing pig

The aim of the experiment was to test the theory that accustoming pigs to a high-fat diet causes exaggerated gastric inhibitory polypeptide (GIP) secretion in response to a high-fat meal, and to determine whether hypersecretion of GIP could be related to an increase in the GIP content of the small intestine. Twenty-four pigs were fed one of three dietary regimens for 11 weeks: a high-carbohydrate diet (CL), or a high-fat diet (FL), both fed at 1.46 MJ gross energy (GE)/kg live weight0.75 per d, or a high-fat diet (FH) fed at 2.10 MJ GE/kg live weight0.75 per d. At the end of the period two acute tests were performed. For acute test 1 the accustomed meal (diets CL, FL and FH) and for acute test 2 a standard high-fat meal (diet FL) were given; blood samples were taken during the next 5 h and analysed for GIP, insulin and glucose. Integrated increases in hormone and glucose levels were compared by analysis of variance (0-300 min). In acute test 1 there were significantly different plasma GIP concentrations between groups (CL greater than FH greater than FL; P less than 0.05). Plasma insulin concentrations were significantly higher in group CL compared with groups FL and FH (P less than 0.002). There were no differences in glucose levels. In acute test 2 integrated increases in plasma GIP (0-300 min) concentrations were not significantly different; however, GIP (0-45 min) concentrations were significantly higher in group FH than in groups CL and FL (P less than 0.05). There were no differences in plasma insulin concentrations. Plasma glucose (0-300 min) concentrations were significantly higher in groups FL and FH compared with group CL (P less than 0.05). The GIP content of tissue samples taken at the end of the experiment from the duodenum, jejunum, upper and lower ileum decreased significantly in a proximal to distal direction (P less than 0.001). Diet FH significantly increased the average GIP content of the small intestine compared with diets CL and FL (P less than 0.05). It is concluded that fat meal-stimulated GIP secretion was enhanced by increased feeding level during a pre-treatment phase, possibly due to an increase in GIP synthesis in the small intestine. The high-fat diet caused glucose intolerance after a high-fat meal. This may be due in part to the action of dietary fat on glucose transport and metabolism.

Experience affects exercise-induced changes in catecholamines, glucose, and FFA.

The interference of the experimental conditions on the exercise-induced alterations in plasma catecholamines, plasma free fatty acids, and glucose and insulin concentrations was investigated in rats. Exercise consisted of strenuous swimming against a countercurrent (0.22 m/s) for 15 min in a pool with water of 33 degrees C. Before, during, and after swimming, blood samples were taken through a permanent heart catheter. The blood component levels in rats that were confronted with exercise for the very first time were compared with the levels in rats that were well accustomed to the exercise conditions. The very first time rats swam caused an enhanced release of epinephrine from the adrenal medulla and a reduced output of norepinephrine from the sympathetic nerve endings. Furthermore, in the first time swim group, blood glucose levels were higher and plasma free fatty acid concentrations were lower compared with the well-accustomed animals. There were no differences in plasma insulin concentrations. It is concluded that the experimental conditions may interfere considerably with the hormonal and metabolic response to exercise. Furthermore the results reinforce the idea that the two parts of the sympathoadrenal system are functionally and metabolically dissociated.

Direct assessment of splanchnic uptake and metabolic effects of human and porcine insulin.

The hepatic vein catheterization technique was used to quantitate the splanchnic uptake and the metabolic effects of biosynthetic human insulin (BHI) and porcine insulin (PI) in normal man. BHI and PI were infused into a peripheral vein (0.9-1.3 mU kg-1 min-1) for 60 min together with SRIH (0.6 mg/h) to inhibit endogenous insulin secretion and glucose to induce moderate hyperglycemia (9-10 mmol/liter). During the infusion period, arterial-hepatic venous difference of plasma C-peptide as well as splanchnic C-peptide output fell by more than 98% indicating virtually complete cessation of endogenous insulin release. Under these conditions, the arterial-hepatic venous differences in plasma insulin concentrations represent a valid and direct measurement of splanchnic insulin uptake. During BHI infusion, arterial insulin levels rose to 82 +/- 11 (SE) microU/ml (range: 33-105 microU/ml). Splanchnic insulin uptake paralleled the rise of arterial insulin, reaching 430 +/- 72 microU kg-1 min-1 at 60 min. No appreciable difference between BHI and PI was demonstrable. A highly significant correlation between arterial insulin concentrations and splanchnic insulin uptake was found (r = 0.816; P less than 0.001). Accordingly, both fractional splanchnic insulin extraction and splanchnic insulin clearance remained unchanged throughout insulin infusion and averaged 70 +/- 4% and 5.3 +/- 2 ml kg-1 min-1, respectively. With BHI infusion, splanchnic glucose balance (-8.5 +/- 0.9 mumol kg-1 min-1, basal) became positive (7.3 +/- 1 mumol kg-1 min-1). In contrast, basal splanchnic lactate uptake was inhibited by BHI and there was lactate production (from 3.4 +/- 0.9 to -1.7 +/- 1.4 mumol kg-1 min-1). Similar changes in splanchnic glucose and lactate metabolism occurred during PI infusion. These studies indicate that: 1) A considerable amount of insulin (70 +/- 4%) is extracted by the splanchnic bed on a single passage, after exogenous administration of either human insulin or PI; 2) over a physiological range of insulin concentrations (33-105 microU/ml) a linear relationship exists between arterial insulin concentrations and splanchnic insulin removal; and 3) BHI and PI do not differ appreciably with respect to their uptake and metabolic effects at the splanchnic level.

Insulin secretion in the spiny mouse (Acomys cahirinus). Dose and time kinetic studies with glucose in vivo and in vitro.

Plasma insulin responses to the intravenous injection of glucose in the doses of 0.5, 1.5, and 3.0 gm./kg. were compared in spiny mice (Acomys cahirinus) and weight-matched Swiss albino mice. The mean early (two-minute) plasma insulin response was significantly lower in Acomys at all doses of glucose injected; whereas, at later times (5, 15, and 30 minutes), differences in plasma insulin concentrations in the two species of mice were smaller or nonexistent. Plasma glucose clearance was significantly less in the Acomys. In terms of glucose dose kinetics, there was a decreased capacity of the mean plasma insulin response in Acomys compared with albino mice at two minutes; whereas, at later times, the mean dose response curve for Acomys was shifted to the right of that for albino mice, indicating a decreased sensitivity to glucose in the Acomys. There was, however, a large variation between the plasma insulin responses of the eight individual Acomys mice tested. There was a significant correlation in individual Acomys between the plasma insulin response, expressed as an insulinogenic index, integrated over the thirty minutes after injection of glucose 3.0 gm./kg. in vivo, and the insulin released from pancreatic islets obtained from the corresponding Acomys and perifused for thirty minutes with glucose 1,000 mg./100 ml. in vitro (r = 0.77, p less than 0.05). It is concluded that the rate and magnitude of the insulin response to glucose in an individual Acomys reflects mainly the degree of sensitivity to glucose of the pancreatic beta cells in that animal.

Plasma and Pancreatic Insulin Concentrations in Adult Squirrel and Rhesus Monkeys

Squirrel and rhesus monkeys were given oral glucose (4 gm./kg.), intravenous glucose (0.4 gm./kg.), intravenous glucose and tolbutamide (0.4 gm./kg. glucose and 50 mg./kg. tolbutamide), or intravenous tolbutamide (15 and 50 mg./kg.). There was delayed disposal of the relatively large doses of orally administered glucose in squirrel monkeys, contrasted with rhesus monkeys. Differences in glucose metabolism between the two species were less apparent during the other tests. Concentrations of plasma -insulin were significantly lower in squirrel than in rhesus monkeys during all of the stimulatory tests, except during the infusion of the lower dose of tolbutamide, when levels in both were relatively low. In contrast, pancreatic islet morphology and concentrations of pancreatic insulin did not differ significantly between the two groups, suggesting that differences in plasma insulin concentrations during stimulatory tests might have been the result of differences in insulin secretory rates. In our group of squirrel monkeys, we could not recognize two populations with respect to any of the parameters studied.