Blood flow in skin, subcutaneous adipose tissue and skeletal muscle in the forearm of normal man during an oral glucose load

Blood flow to the forearm, and the subcutaneous tissue and skin in the forearm were measured by strain gauge plethysmography, 133Xe-elimination and Laser Doppler flowmetry during an oral glucose load (I g glucose kg-1 lean body mass) and during control conditions. The forearm blood flow remained constant during both experiments. Glucose induced a two-fold vasodilatation in subcutaneous tissue. In skin, glucose induced a relative vasodilatation and later a relative vasoconstriction compared with control experiments. When estimated from forearm blood flow and subcutaneous and skin blood flows, muscle blood flow decreased about 20-30% during both experiments. Proximal nervous blockade did not abolish the glucose-induced vasodilatation in subcutaneous tissue. In the glucose experiment, arterial glucose concentration increased to 7.8 +/- 1.17 mmol l-1 30 min after the load was given and then decreased to 4.5 +/- 0.34 mmol l-1 at the end of the experiment. In the control experiments glucose concentration was constant. Arterial noradrenaline concentration increased significantly from 1.0 +/- 0.13 to about 1.5 +/- 0.3 nmol l-1 120 min after glucose and remained at this level during the experiment. Similarly adrenaline increased from 0.16 +/- 0.11 to about 0.4 +/- 0.16 nmol l-1 180 min after glucose. It is hypothesized that the vasodilating effect of glucose in subcutaneous tissue is secondary to metabolic events connected to glucose uptake and energy deposition in adipose tissue.     

Secretin potentiates cholinergically induced glucagon secretion in the mouse

Glucagon secretion is stimulated by cholinergic activation, and it is known that the polypeptides VIP (vasoactive intestinal polypeptide) and GIP (gastric inhibitory polypeptide) both potentiate this cholinergically induced glucagon secretion. In this study, we investigated whether secretin, which shows structural similarities to both VIP and GIP, affects basal and cholinergically induced glucagon secretion in the mouse. Secretin was injected i.v. to mice at dose levels varying from 0.53 to 17 nmol kg-1, and plasma samples were taken at 2, 6 and 10 min following injection. It was found that secretin in this wide dose range did not affect basal glucagon concentrations. When the cholinergic agonist carbachol was injected i.v. at 0.16 mumol kg-1, plasma glucagon levels were elevated; at 2 min at 0.84 +/- 0.04 ng ml-1 compared to 0.31 +/- 0.02 ng ml-1 in controls (P less than 0.001). A combination of carbachol and secretin (4.25 nmol kg-1) enhanced plasma glucagon levels to 1.22 +/- 0.07 ng ml-1. Thus, secretin potentiated carbachol-induced glucagon secretion by 70% (P less than 0.001). Concomitantly, plasma glucose levels were elevated: 10.8 +/- 0.4 mmol l-1, compared to 9.2 +/- 0.4 mmol l-1 in controls (P less than 0.001). We conclude that secretin, while being without effect on basal glucagon secretion, markedly potentiates cholinergically induced glucagon secretion in the mouse, resulting in increased plasma glucose levels.     

The forearm and leg perfusion techniques in man do not give the same metabolic information

The present study evaluates whether forearm and leg perfusion techniques give the same metabolic information. Seven patients hospitalized for operation of uncomplicated disease were investigated pre-operatively in the fasted state, while seven other patients who were on intravenous nutrition were studied in the fed state. Blood flow and the extremity exchange of glucose, lactate, glycerol, free fatty acids and amino acids were measured simultaneously across the forearm and the leg in all individuals. In the fasted state the arteriovenous difference (a-v) of glucose uptake was statistically significant across the forearm while it was statistically insignificant across the leg (0.27 +/- 0.06 vs. -0.04 +/- 0.13 mmol l-1). The a-v differences of glycerol (0.025 +/- 0.028 vs. -0.043 +/- 0.013 mmol l-1) and free fatty acids 0.10 +/- 0.03 vs. -0.10 +/- 0.04 mmol l-1) were positive across the forearm while they were negative across the leg (P less than 0.01). In the fasted state the a-v difference of oxygen uptake (3.93 +/- 0.67 vs. 3.21 +/- 0.44 mmol l-1) and blood flow (4.1 +/- 1.0 vs. 4.0 +/- 0.7 ml min-1 100 g-1) did not differ between the arm and the leg, but the a-v difference in carbon dioxide production was significantly higher (P less than 0.05) across the forearm (2.43 +/- 0.37 vs. 1.29 +/- 0.29 mmol l-1) compared to the leg. In the fed state all the above-mentioned differences between forearm and leg became statistically insignificant. In the fed state the a-v difference of the sum of all amino acids was not significantly different from zero balance across the forearm (-146 +/- 103 mmol l-1) while there was a significant release from the leg (-175 +/- 6 mmol l-1, P less than 0.05). In the fed state the flux of the sum of all amino acids became significantly positive across the arm while it was not significantly different from zero balance across the leg. In the fed state, forearm blood flow was significantly higher than leg blood flow (6.2 +/- 0.5 vs. 4.0 +/- 0.2 ml min-1 100 g-1, P less than 0.001). The results in the present study demonstrate that the metabolic balance across regions of peripheral tissues may simultaneously differ considerably, i.e. being positive across the forearm and negative across the leg. This fact may imply that some previous claims may need reconsideration about 'peripheral tissue metabolism' associated with a certain clinical condition.     

Effects of a three-hour calcium clamp on calcium, phosphate, magnesium and zinc concentrations of human parotid saliva

Ionized (saliva-Ca2+) and total calcium (saliva-CaT), inorganic phosphate (saliva-P), magnesium (saliva-Mg), and zinc (saliva-Zn) levels in parotid saliva were studied in eight healthy volunteers during a 3-h calcium infusion, directly regulated to obtain a pre-settled standardized blood calcium level. Frequent determinations of whole blood ionized calcium (B-Ca2+) were used for continuous adjustments of the calcium infusion rate ('calcium clamp'). Basal B-Ca2+ (1.26 +/- 0.04 mmol X l-1, mean +/- SD) was thus elevated to and maintained at 1.51 +/- 0.05 mmol X l-1 from +30 to +180 min. Saliva samples were taken prior to the infusion and at regular intervals during the infusion period. Saliva-Ca2+ decreased from 0.38 +/- 0.06 to 0.33 +/- 0.05 mmol X l-1 (P less than 0.01) and saliva-Ca2+ as a percentage of saliva CaT from 63 +/- 7% to 53 +/- 10% (P less than 0.001) during the infusion. No changes could be observed in saliva-CaT, saliva-P, saliva-Mg, saliva-Zn, saliva-Na and saliva-K. Possible mechanisms behind these findings might be decreased parathyroid hormone and increased calcitonin concentrations in serum.     

Arterial and venous measurement in resting forearm of metabolic indicators during rest and leg exercise

We compared the levels of various metabolic indicators in arterial and venous forearm blood during maximal treadmill leg exercise, and the subsequent 9 min in nine volunteers aged 31-56 years. At maximal exercise plasma lactate was 13.2 +/- 3.1 mmol l-1 arterially, while venous was 41% lower, but increased more than arterial after exercise. There was a linear relationship between arterial and venous samples during and after exercise, but not at baseline. Plasma pyruvate increased on the arterial side from 49 +/- 8 to 172 +/- 30 mumol l-1 at maximal exercise, maximal venous was 21% lower. Free fatty acids were not different at rest, but decreased during exercise by 52 and 38% on the arterial and venous side. There was no relationship between arterial and venous levels. Changes in these three variables occurred significantly earlier on the arterial side. Arterial cyclic AMP rose from 97.3 +/- 28.4 to 262.7 +/- 67.5 nmol l-1 from rest to exercise, and was linearly inversely related to the decrease in free fatty acids. The mean venous pH was lower than arterial at rest, but was the same as arterial at maximal exercise and after. Thus, venous plasma lactate and pyruvate, but not free fatty acids, are linearly related to arterial measurements during maximal exercise, while pH is identical. Non-working muscle modifies exercise-induced changes, and therefore venous and arterial forearm blood sampling give more information than either alone.     

Gastroenteropancreatic hormonal changes during exercise

Peripheral plasma concentrations of gastroenteropancreatic peptides were measured during a 3-h period of bicycle exercise at 40% of maximal oxygen uptake in six normal men. Marked increases (P < 0.02) were found in vasoactive intestinal polypeptide (VIP) [1.8 +/- 0.7 (rest) vs. 22.3 +/- 5.4 pmol x l-1 (mean +/- SE) (3 h)], secretin (0.5 +/- 0.5 vs. 11.1 +/- 2.7 pmol x l-1), pancreatic polypeptide (PP) (4.0 +/- 1.5 vs. 46.3 +/- 11.5 pmol x l-1), somatostatin (SRIF) (12.8 +/- 1.2 vs. 17.7 +/- 0.6 pmol x l-1), whereas no changes occurred in gastric inhibitory polypeptide (37.3 +/- 5.9 vs. 39.2 +/- 9.8 pmol x l-1). Immunoreactive insulin and C-peptide decreased from 0.08 +/- 0.004 and 0.39 +/- 0.03 pmol x l-1, respectively, to 0.04 +/- 0.003 (P < 0.005) and 0.13 +/- 0.02 (P < 0.001). The significant decrease in C-peptide and in the C-peptide-to-insulin molar ratio indicate decreased insulin secretion and clearance, respectively, during exercise. Plasma glucose decreased [5.0 +/- 0.1 (rest) vs. 4.2 +/- 0.3 mmol.l-1 (3 h)] (P < 0.01). During 3 h of rest, none of the measured parameters had changed. The marked exercise-induced changes in plasma concentrations of PP, secretin, VIP, and SRIF are provocative. We know in detail neither the stimuli for the release of these peptides nor their physiological role during exercise.     

壳聚糖胰岛素微球在糖尿病大鼠中的降糖作用研究

我们观察了壳聚糖为载体的胰岛素微球的口服制剂对链脲菌素致糖尿病大鼠的降血糖作用.用扫描电镜观察正常大鼠管饲壳聚糖胰岛素微球后1、2、3、7d微球在大鼠体内的分布.18只链脲佐菌素致糖尿病大鼠被随机分成3组壳聚糖胰岛素微球管饲组(120U/kg,n=6);诺和灵中效胰岛素皮下注射组(24U/kg,n=6),空白对照组(管饲等容积的蒸馏水,n=6).另有5只正常大鼠作为正常对照组(管饲等容积的蒸馏水,n=5).分别测定4组大鼠用药前后的血糖值,并做组间分析比较.结果表明(1)壳聚糖胰岛素微球能通过大鼠的小肠吸收,并靶向分布于小肠、肝、脾等器官.(2)壳聚糖胰岛素微球管饲组在管饲微球后第1天,糖尿病大鼠的血糖从24.7±3.2mmol/L下降至16.9±5.5mmol/L,第2天降至最低12.1±5.7mmol/L,第3天开始逐渐回升至用药前水平,血糖最大下降幅度为50.2%.诺和灵中效胰岛素皮下注射组注射胰岛素后,糖尿病大鼠的血糖从25.2±3.8mmol/L下降至10.4±5.2mmol/L,第2天开始逐渐回升至用药前水平,血糖最大下降幅度为58.7%.两组下降幅度比较无统计学差异(P＞0.05).而空白对照组和正常对照组大鼠的血糖无明显变化,但它们分别和前两组比较,具有统计学差异(P＜0.001).因此,我们认为对链脲菌素致糖尿病大鼠,管饲壳聚糖胰岛素微球具有一定程度的降糖效果.     

Plasma lipid and lipoprotein profile in elderly female runners.

Plasma lipid and lipoprotein profiles were compared in elderly female runners (RU: n = 15, aged 66 +/- 5 years, body fat 20 +/- 4%, training distance 35 +/- 15 km week-1, VO2max 36 +/- 4 ml kg-1 min-1, mean +/- SD) and age-matched untrained women (UT: n = 28, 66 +/- 4 years, body fat 26 +/- 6%, VO2max 26 +/- 3 ml kg-1 min-1). There were insignificant differences in total cholesterol (RU: 5.04 +/- 0.60 vs. UT: 5.48 +/- 0.85 mmol l-1), HDL-cholesterol (RU: 1.97 +/- 0.41 vs. UT: 1.91 +/- 0.36 mmol l-1) and LDL-cholesterol (RU: 2.72 +/- 0.59 vs. UT: 3.03 +/- 0.80 mmol l-1) between the two groups. Plasma triglyceride concentration of the runners was significantly lower than that of the untrained women (RU: 0.80 +/- 0.27 vs UT: 1.14 +/- 0.36 mmol l-1, P less than 0.01). No difference was observed in the LDL-cholesterol/HDL-cholesterol ratio between the two groups (RU: 1.45 +/- 0.51 vs UT: 1.64 +/- 0.53 units). These results suggest that regularly performed running of 35 km week-1 in elderly women does not further elevate their HDL-cholesterol level which is already high compared to the levels found in elderly men. However, elderly female runners appear to be protected against age-related increases in the levels of triglyceride and LDL-cholesterol.     

Plasma noradrenaline levels and thermogenic responses to injected noradrenaline in the conscious rat

The changes in metabolic rate (MR) and plasma noradrenaline (NA) were studied in rats injected with NA either subcutaneously (S.C.) or intravenously (I.V.). Injection of NA (400 micrograms kg-1 S.C.) raised the MR by 54.0 +/- 10.2% above baseline and the levels of plasma NA were higher in right atrial venous plasma (147.0 +/- 6.6 nmol l-1) than in arterial plasma (54.4 +/- 6.6 nmol l-1) 90 min after the injection. There was no significant increase in MR in response to the infusion of 0.4 microgram NA min-1 kg-1 but significant responses occurred (P less than 0.01) with infusion of 1.5, 3.0, 4.0 and 8.0 micrograms min-1 kg-1. The maximum increase in MR was 90.3 +/- 7.4% during the 3.0 micrograms min-1 kg-1 infusion. The arterial plasma NA levels were directly proportional to the NA infusion rate, 18.0 +/- 8.3, 72.4 +/- 14.3, 159.5 +/- 28.4, 222.3 +/- 62.1 and 590.0 +/- 172.1 nmol l-1 for the 0.4, 1.5, 3.0, 4.0 and 8.0 micrograms min-1 kg-1 infusion respectively. This study shows that high plasma levels of NA are needed to induce thermogenesis when NA is administered either S.C. or I.V.     

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type-2.

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type-2 diabetic patients. The study was performed in 16 insulin treated type-2 diabetics (eight male/eight female, age 47 +/- 3 years, HbA1c 7.2 +/- 0.2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8.7 +/- 1.1 to 15.3 +/- 1.0 mmol l-1 (P<0.001) postprandially. This resulted in (i) a significant increase of resting blood flow (3.4 +/- 0.3 to 4.8 +/- 0.4 ml min-1 100 ml-1, P<0.01) and (ii) in a reduced peak reactive hyperaemia (52.3 +/- 7.4 to 36.8 +/- 4.3 ml min-1 100 ml-1, P<0.005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non-diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type-2 diabetic patients.     

Altered skeletal muscle glucose transport and blood lipid levels in habitual cigarette smokers.

We determined whether habitual cigarette smoking alters insulin-stimulated glucose transport and GLUT4 protein expression in skeletal muscle. Vastus lateralis muscle was obtained from 10 habitual cigarette smokers and 10 control subjects using an open muscle biopsy procedure. Basal 3-O-methylglucose transport was twofold higher (P < 0.01) in muscle from habitual smokers (0.05 +/- 0.08 vs. 1.04 +/- 0.19 mumol ml-1 h-1; controls vs. smokers respectively). Insulin (600 pmol l-1) increased glucose transport 2.6-fold (P > 0.05) in muscle from control subjects, whereas no significant increase was noted in habitual smokers. Skeletal muscle GLUT4 protein expression was similar between the groups. FFA levels were elevated in the smokers (264 +/- 49 vs. 748 +/- 138 mumol l-1 for control subjects vs. smokers; P < 0.05), and serum triglyceride levels were increased in the smokers (0.9 +/- 0.2 vs. 2.3 +/- 0.6 mmol l-1 for control subjects vs. smokers; P < 0.05). Skeletal muscle carnitine palmitil (acyl) transferase activity was similar between the groups, indicating that FFA transport into the mitochondria was unaltered by cigarette smoking. In conclusion, cigarette smoking appears to have a profound effect on glucose transport in skeletal muscle. Basal glucose transport is markedly elevated, whereas insulin-stimulated glucose transport is impaired. These changes cannot be explained by altered protein expression of GLUT4, but may be related to increased serum FFA and triglyceride levels. These findings highlight the importance of identifying habitual cigarette smokers in studies aimed at assessing factors that lead to alterations in lipid and glucose homeostasis in people with non-insulin-dependent diabetes mellitus (NIDDM).     

Effect of hypoxia on glucose metabolism in human skeletal muscle during exercise

The effect of respiratory hypoxia on muscle glucose metabolism during short-term dynamic exercise has been investigated. Eight men cycled for 5 min at 120 +/- 6 W (mean +/- SE), which corresponded to 50% of maximal O2 uptake during normoxia (N), breathing air (N) on one occasion and 11% O2 (hypoxia-H) on the other. Biopsies were taken from the quadriceps femoris muscle before and after exercise. Oxygen uptake during exercise was not affected by H. The arterial blood glucose concentration during N exercise remained constant, but increased from 4.62 +/- 0.11 mmol l(-1) at rest to 5.22 +/- 0.19 mmol l-1 at the end of H exercise (P less than 0.05 vs N exercise). The intracellular glucose content at rest was low and did not change during N exercise, but was four times higher after exercise during H vs N (P less than 0.01). Glucose 6-P increased under both conditions but significantly more during H (P less than 0.01), while glucose 1,6-P2 was not significantly different between treatments either at rest or after exercise. It is concluded that: (1) glucose uptake by skeletal muscle during short-term exercise. It is concluded that: (1) glucose uptake by skeletal muscle during short-term exercise during H is not associated with a stoichiometric glucose utilization; (2) the inhibition of hexokinase during H (evidenced by increase in muscle glucose) is due primarily to the increase in glucose 6-P; and (3) glucose 1,6-P2 is of minor importance for the regulation of contraction-mediated flux through hexokinase in human skeletal muscle.     

Effect of acute acidosis and alkalosis on leucine kinetics in man.

The effects of acute pH changes on whole body leucine kinetics (1-13C-leucine infusion technique) were determined in normal subjects. Plasma insulin, glucagon, and growth hormone concentrations were kept constant by somatostatin and replacement infusions of the three hormones. When acidosis was produced by ingestion of NH4Cl (4 mmol kg-1 p.os; n = 8) arterialized pH decreased within 3 h from 7.39 +/- 0.01 to 7.31 +/- 0.01 (P less than 0.001) and leucine plasma appearance increased by 0.13 +/- 0.04 mumol kg-1 min-1 (P less than 0.02); in contrast, when alkalosis was produced by intravenous infusion of 4 mmol kg-1 NaHCO3 (n = 7, pH 7.47 +/- 0.01), leucine plasma appearance decreased by -0.09 +/- 0.04 mumol kg-1 min-1 (P less than 0.01 vs. acidosis). Whole body leucine flux also increased during acidosis compared to alkalosis (P less than 0.05), suggesting an increase in whole body protein breakdown during acidosis. Apparent leucine oxidation increased during acidosis compared to alkalosis (P = 0.05). Net forearm leucine exchange remained unaffected by acute pH changes. Plasma FFA concentrations decreased during acidosis by -107 +/- 67 mumol l-1 (P less than 0.05) and plasma glucose increased by 1.90 +/- 0.25 mmol l-1 (P less than 0.02); in contrast, alkalosis resulted in an increase in plasma FFA by 83 +/- 40 mumol l-1 (P less than 0.02; P less than 0.01 vs. acidosis), suggesting an increase in lipolysis; plasma glucose decreased compared to acidosis (P less than 0.01). The data demonstrate that acute metabolic acidosis and alkalosis, as they occur in clinical conditions, influence protein breakdown, and in the opposite direction, lipolysis.     

Restoration of hemorrhaged plasma volume by gastrointestinal fluid in the dog

Conscious, intact and splenectomized, male dogs were hemorrhaged 35 percent of their blood volumes (23 +/- 3 and 25 +/- 4 ml/kg, respectively) from carotid loop cannulas. Isotonic saline or glucose solutions were administered by gastric tube in volumes equal to the blood volume hemorrhaged. Plasma volume, mean arterial blood pressure, venous hematocrit, plasma protein concentration, and interstitial fluid pressure were monitored after hemorrhage and after fluid treatment. The magnitudes of plasma volume restoration 8 h after hemorrhage in the nontreated dogs averaged 56 +/- 9 percent of the hemorrhaged volume and did not differ significantly between intact and splenectomized dogs. Plasma volumes, however, were increased significantly by enterally administered fluids. The maximum rates of plasma volume restoration occurred within the 1st h after fluid treatment. Approximately 46 percent and 28 percent of the hemorrhaged plasma volume was replaced by saline and glucose solutions, respectively, during this period. Results support the hypothesis that fluid is absorbed from the gastrointestinal tract following hemorrhage, and that enterally administered fluids restore plasma volume at a rate and to an extent exceeding that provided by net interstitial fluid exchange alone.     

Glucose tolerance and physical activity in a health survey of middle-aged subjects

Glucose tolerance and reported physical leisure time activity were studied in middle-aged, 47-54 years old, subjects in a health survey. The mean 2-hour blood glucose value after 75 g oral glucose tolerance tests was higher (p less than 0.001) in 682 subjects with a lower degree of leisure time activity than in 125 subjects who were regularly active at least 2-3 hours per week. The mean 2-hour glucose values in the inactive and active groups, respectively, were 4.61 and 4.09 mmol X l-1 after adjustment for the influence of age, body mass index, smoking and physical job activity by analysis of covariance. The difference between adjusted mean 2-hour glucose values was also significant (p less than 0.001) in the subgroups of 280 low leisure time activity males (4.53 mmol X l-1) and 91 active males (3.93 mmol X l-1). Thus, a relation between physical leisure time inactivity and raised post load blood glucose values seems to exist in the general population.     

Influence of glucose and fructose ingestion on the capacity for long-term exercise in well-trained men

The aim of the present study was to examine the influence of glucose and fructose ingestion on the capacity to perform prolonged heavy exercise. Eight well-trained healthy volunteers exercised on a bicycle ergometer at 68 +/- 3% of their VO2 max until exhaustion, on three occasions, with 8-day intervals. During the exercise they ingested either glucose (250 ml, 7%), fructose (250 ml, 7%) or water (250 ml) every 20 min in a double-blind randomized study design. Arterial blood samples were collected at rest and during exercise for the determination of substrates and hormones. Muscle glycogen content (m. quadriceps femoris) was measured before and after exercise. The duration of exercise lengthened with repeated exercise (3rd test: 136 +/- 13 min v. 1st test: 110 +/- 12 min, P less than 0.01). Corrected for the sequence effect, total work time until exhaustion was significantly longer with glucose (137 +/- 13 min) than with either fructose (114 +/- 12 min) or water (116 +/- 13 min) (both P less than 0.01). When glucose or fructose was ingested, the arterial plasma glucose concentration was maintained at the normoglycaemic level; with water ingestion, plasma glucose values fell during exercise in seven subjects and remained at the resting level in the eighth subject. The muscle glycogen concentration was 467 +/- 29 mmol kg d.w.-1 at rest and fell to approximately half the initial value at exhaustion. In the subgroup of seven subjects in whom glucose values decreased with water intake, the mean rate of glycogen degradation was significantly lower (P less than 0.05) with the ingestion of glucose (1.3 +/- 0.4 mmol kg d.w.-1 min-1) as compared to fructose (2.1 +/- 0.5 mmol kg d.w.-1 min-1) or water (2.3 +/- 0.5 mmol kg d.w.-1 min-1). Intermittent glucose ingestion (3 X 17.5 g h-1) during prolonged, heavy bicycle exercise postpones exhaustion and exerts a glycogen-conserving effect in the working muscles. In contrast, fructose ingestion during exercise maintains the glucose concentration at the basal level but fails to influence either muscle glycogen degradation or endurance performance.     

Galanin: effects on basal and stimulated insulin and glucagon secretion in the mouse

Galanin was recently demonstrated to be a neuropeptide in intrapancreatic nerves. In this study, the effects of galanin on basal and stimulated insulin and glucagon secretion in the mouse were investigated. Galanin, injected intravenously at dose levels ranging from 0.53 to 8.5 nmol kg-1, markedly lowered basal plasma insulin levels and transiently increased basal plasma glucagon levels. Furthermore, galanin induced hyperglycaemia: plasma glucose levels were 11 +/- 0.2 mmol l-1 2 min after injection of galanin (4.25 nmol kg-1) compared with 9.3 +/- 0.3 mmol-1 in controls (P less than 0.001). Galanin also impaired the plasma insulin response to either glucose or the cholinergic agonist carbachol. Thus, galanin (4.25 nmol kg-1) inhibited the plasma insulin response to glucose by 65% (P less than 0.001), and that to carbachol by 85% (P less than 0.001). Moreover, glucose abolished the galanin-induced plasma glucagon response. Also, galanin and carbachol exerted additive stimulatory effects on glucagon levels. It is concluded from this study in mice that galanin inhibits basal and stimulated insulin secretion, stimulates glucagon secretion, and induces hyperglycaemia. It is suggested that the intrapancreatic neuropeptide galanin is of importance in the regulation of both insulin and glucagon secretion.     

The effect of asymptomatic nocturnal hypoglycemia on glycemic control in diabetes mellitus

To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.     

Cholecystokinin-stimulated insulin secretion and protein kinase C in rat pancreatic islets

In isolated rat pancreatic islets, the possible involvement of protein kinase C in cholecystokinin-8-stimulated insulin secretion was investigated. In islets exposed for 24 hours to the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (500 nmol l-1), a procedure known to down-regulate islet protein kinase C-activity, the insulinotropic effect of cholecystokinin-8 (10(-7) mol l-1) was partially reduced (by 34 +/- 8%, P less than 0.001). In contrast the insulinotropic response to acute exposure to 12-O-tetradecanoyl phorbol 13-acetate (10(-6) mol l-1) was totally abolished (P less than 0.001), whereas the insulin response to glucose (8.3 mmol l-1) was not affected. In normal islets, the protein kinase C-inhibitor, staurosporine, inhibited 12-O-tetradecanoyl phorbol 13-acetate- and glucose-stimulated insulin secretion (P less than 0.01), but was without effect on cholecystokinin-8-stimulated insulin release. Furthermore, in normal islets, cholecystokinin-8 had no effect on insulin release at a low glucose level (3.3 mmol l-1). However, at this low glucose level, cholecystokinin-8 clearly potentiated insulin release induced by acute exposure to 12-O-tetradecanoyl phorbol 13-acetate (10(-8) -10(-6) mol l-1, P less than 0.001). This potentiating effect was abolished by the removal of extracellular Ca2+. It is concluded that the insulinotropic effect of cholecystokinin-8 in rat islets is partially mediated by the protein kinase C pathway. Furthermore, the lack of effect of cholecystokinin-8 on insulin secretion at a low glucose level might be explained by an insufficient activation of protein kinase C under these conditions.     

Actively circulating blood volume in endotoxin shock measured by indicator dilution.

To estimate the size of the actively circulating blood volume of splenectomized dogs during control conditions and after endotoxin infusion, the pattern of concentration changes of 51Cr-labeled erythrocytes and 125I-labeled albumin was monitored. A dual exponential equation was fitted to the data. The total red blood cell and albumin volumes of distribution were determined from the slow exponential disappearance curves. The active red blood cell and albumin volumes were 89.8 +/- 5.3% and 92.0 +/- 2.0% of the total volumes, respectively. After endotoxin shock (mean arterial blood pressure 49.1 +/- 17.8 mmHg) the active volumes fell to only 60.0 +/- 10.3% and 56.2 +/- 20.0% of the total volumes, respectively. The fast-mixing time constants were similar (3.1 +/- 1.4 min and 2.5 +/- 2.7 min, respectively) and did not change significantly during the endotoxin shock, indicating that the albumin tag mixed into its larger volume of distribution as rapidly as the cells mixed into their indicated volume. We conclude that 1) an active blood volume can be distinguished, 2) it decreases for both red blood cells and albumin in endotoxin shock, and 3) a major part of the "extravascular plasma volume," as estimated by albumin dilution, is in the actively circulating circulation.