Fall In Blood Glucose Concentration Research Articles

Blood Glucose Profiles in Diabetic Rodents Using Different Insulin Preparations

The aim of the present study was to evaluate several long-acting insulin preparations for their ability to normalize the blood glucose profile of rats and mice with streptozocin-induced diabetes mellitus. The single injection of a long-acting zinc insulin (CAS 8049-62-5) suspension or insulin glargine (CAS 160337-95-1) in both species induced a steep to moderate fall in blood glucose concentration. Blood glucose was then normalized for 2-3 h, until 3 h after insulin injection blood glucose concentration tended towards levels before insulin application. In contrast, implants produced with a mixture of human insulin and palmitic acid micro-crystals normalized blood glucose profile over 24 h in both species at least 30 days after implantation. Therefore, these implants with a sustained release of insulin are suitable to control the blood glucose in diabetic rats and mice.

Maintenance of blood glucose level under intensive mental activities: episodic moderate drinkers versus non-drinkers

BackgroundThe benefits of alcohol, especially to the functioning ofthe hearth and circulatory system have always beenrecognized by many researchers world-wide [1]. Butbesides, these positive effects, alcohol use, even in mod-erate amounts can be detrimental under certain condi-tions. Several studies have recognized the hypoglycemiceffect of alcohol use in excessive doses. Centuries ago,Krebs and fellows admitted that acute alcohol intake inexcessive doses results in hypoglycemia [2,3]. However,little is still known about the aftereffects of alcohol atlow doses, even after a week’s interval of moderatedrinking.AimWe examine the efficiency of glucose homeostasis con-trol of non-drinkers and episodic moderate drinkers,after approximately one week interval of moderatedrinking and under intensive mental activities.Materials and methodsThe Ethics Committee approved the study protocoland informed consents were obtained from the volun-teers after the aims and objectives of the study hadbeen explained. The study took 6-hours (on fasting),involving male students (5 non-drinkers and 8 episodicmoderate drinkers that have abstained from alcoholdrinks of any composition for at least the last sevendays before the study). Blood glucose concentration(BGC) was measured at 2 hours interval, includinginitial BGC. Various questionnaires - AUDIT, texts andquestions, neuropsychological questionnaires, tests onvisual, auditory, operative short-term memory andattention (using Anfimov geometric tables) were usedas a measure. The Pearson and Student’st-testswereemployed for statistical analysis of results. The prob-ability value for significance was set at p < 0.05.ResultsSignificant decrease in the effectiveness of active atten-tion and a faster development of fatigue after 4-6 hoursof mental activities in episodic moderate drinkers, com-pared to non-drinkers was statistically proven. Disordersin episodic moderate drinkers are retained within a per-iod of 7-10 days after moderate alcohol use. The non-drinkers had increasing BGC in relation to their initiallevel in all phases of the experiment (ð < 0.001).Increase in BGC of alcohol users was observed onlywithin the first 2 hours (p < 0.05). Thereafter, a signifi-cant fall in BGC was observed in the 4-6 hrs of theexperiment in relation to the BGC of anon-drinkers andits level after 2 hours. Episodic moderate drinkers had26 times higher errors on various tests than the abstai-ners (p < 0.001). The errors made on various testsincreased with decrease in BGC (r = -0.83; p < 0.01).ConclusionsThis is the first study involving male volunteers to showthat alcohol use, even episodic (1-2 times/month) insmall doses (23 ± 8 ml/person/session), after 7-10 daysof alcohol intake, is accompanied by long-term glucosehomeostasis disorders, leading to cognitive function dis-turbances and a decrease in the effectiveness of mentalactivities. Significant decrease in BGC in episodic mod-

Carbon dioxide sensitivity during hypoglycaemia‐induced, elevated metabolism in the anaesthetized rat

We have utilized an anaesthetized rat model of insulin-induced hypoglycaemia to test the hypothesis that peripheral chemoreceptor gain is augmented during hypermetabolism. Insulin infusion at 0.4 U kg (-1)min(-1) decreased blood glucose concentration significantly to 3.37 +/- 0.12 mmol l(-1). Whole-body metabolism and basal ventilation were elevated without increase in P(a,CO(2)) (altered non-significantly from the control level, to 37.3 +/- 2.6 mmHg). Chemoreceptor gain, measured either as spontaneous ventilatory airflow sensitivity to P(a,CO(2)) during rebreathing, or by phrenic minute activity responses to altered P(a,CO(2)) induced by varying the level of artificial ventilation, was doubled during the period of hypermetabolism. This stimulatory effect was primarily upon the mean inspiratory flow rate, or phrenic ramp component of breathing and was reduced by 75% following bilateral carotid sinus nerve section. In vitro recordings of single carotid body chemoafferents showed that reducing superfusate glucose concentration from 10 mM to 2 mM reduced CO(2) chemosensitivity significantly from 0.007 +/- 0.002 Hz mmHg(-1) to 0.001 +/- 0.002 Hz mmHg(-1). Taken together, these data suggest that the hyperpnoea observed during hypermetabolism might be mediated by an increase in the CO(2) sensitivity of the carotid body, and this effect is not due to the insulin-induced fall in blood glucose concentration.

Responses of plasma glutamine, free tryptophan and branched-chain amino acids to prolonged exercise after a regime designed to reduce muscle glycogen.

Prolonged exercise can elicit a reduction in the plasma glutamine concentration and an increase in the plasma concentration ratio of free tryptophan (FTrp) to branched-chain amino acids (BCAA). The purpose of this investigation was to study the effects of a 60-min bout of vigorous treadmill running with dietary manipulation on plasma concentrations of glutamine, FTrp and BCAA after an exercise and diet regime designed to reduce muscle glycogen. Seven male distance runners [mean (SD) age: 29.3 (2.1) years; VO2max: 62.7 (3.3) ml.kg-1.min-1] acted as subjects. Each undertook a regime designed to reduce muscle glycogen, then performed a 60-min treadmill run (75% VO2max) under two dietary conditions: after a 14-h fast (fasted) and after ingestion of a high carbohydrate meal (30 kJ.kg-1: 80% carbohydrate, 10% protein, 10% fat) 3 h before running (fed). Plasma concentrations of glutamine, FTrp, BCAA, free fatty acids (FFA), glycerol and glucose were measured 5 min before and 5 min after the run, under each dietary condition. Plasma glutamine did not change in response to exercise when fasted (P > 0.05), but increased when fed (P = 0.007). Plasma FTrp increased under both dietary conditions (P < 0.001), but the magnitude of this increase was greater when fasted than when fed (P < 0.001). Plasma BCAA did not change under either dietary condition (P < 0.05). Increases in the plasma FTrp/BCAA ratio reflected increases in plasma FFA and glycerol concentrations (P < 0.001; both dietary conditions) and these changes were all greater under fasted conditions when a fall in blood glucose concentration was observed (P = 0.007). These data emphasise the importance of dietary carbohydrate intake between repeated bouts of prolonged exercise on responses of plasma glutamine, FTrp and BCAA during subsequent exercise.

Tumor necrosis factor enhances glucose uptake by peripheral tissues.

Anesthetized dogs received a constant intravenous infusion of tumor necrosis factor (TNF) or saline over 6 h. Glucose kinetics were studied by determining the rate of glucose turnover and hindlimb substrate flux. Cardiovascular responses were monitored and concentrations of counterregulatory hormones were also measured. TNF infusion caused a fall in blood glucose concentration from 4.6 +/- 0.1 to 3.9 +/- 0.2 mmol/l by 6 h (P less than 0.05). This mild hypoglycemia was associated with increased circulating levels of cortisol, glucagon, and epinephrine. The rate of glucose production increased from 26.5 +/- 2.1 to 32.5 +/- 0.7 mumol.min-1.kg body wt-1 (P less than 0.05) over the 6-h infusion period; this response was associated with increased glucose disappearance (26.4 +/- 2.2 to 32.7 +/- 0.9 mumol.min-1.kg body wt-1, P less than 0.05) and enhanced clearance (5.7 +/- 0.5 to 9.0 +/- 0.6 ml.min-1.kg body wt-1, P less than 0.05). As blood glucose levels fell, hindlimb glucose uptake and glucose clearance increased markedly in TNF-infused animals as compared with controls despite a 50% fall in mean serum insulin concentration. The exchange of lactate, pyruvate, and total amino acid nitrogen across the hindlimbs was similar in both groups of animals. However, arterial concentrations of lactate and pyruvate rose to two to three times their initial values. The hypoglycemia associated with the infusion of TNF results from a disparity between the rate of glucose appearance and disappearance. There is an increased uptake of glucose across the hindlimb; this response appears to be independent of insulin concentrations and may be related to direct effects of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycaemic threshold for changes in electroencephalograms during hypoglycaemia in patients with insulin dependent diabetes

The relation between blood glucose concentration, the symptoms and signs of hypoglycaemia, and electroencephalographic changes in diabetic patients is not known. The effect of hypoglycaemia on brain function was studied in 13 patients with insulin dependent diabetes. During a gradual fall in blood glucose concentration induced by a bolus injection of insulin followed by an intravenous infusion of insulin, during 60 minutes of biochemical hypoglycaemia, and after restoration of normoglycaemia with intravenous glucose electroencephalograms were evaluated continuously by period-amplitude analysis; blood samples were taken every 10 minutes throughout. No changes were seen in electroencephalograms when the blood glucose concentration was above 3 mmol/l. At a median blood glucose concentration of 2.0 (95% confidence interval 1.7 to 2.3) mmol/l alpha activity decreased abruptly in the electroencephalograms concomitant with an increase in theta activity, reflecting neuronal dysfunction in the cortex. When the blood glucose concentration was further lowered changes were observed in the electroencephalograms indicating that deeper brain structures were affected. A normal electroencephalogram was re-established at a blood glucose concentration of 2.0 (1.8 to 2.1) mmol/l. There was no significant correlation between the blood glucose concentration at the onset of changes in the electroencephalograms and age, duration of diabetes, insulin dose, haemoglobin A1c concentration, initial blood glucose concentration, rate of fall in blood glucose concentration, and appearance of symptoms and signs of hypoglycaemia. Changes in electroencephalograms during hypoglycaemia appear and disappear at such a narrow range of blood glucose concentrations that the term threshold blood glucose concentration for the onset of such changes seems justified.

Pituitary apoplexy, the houssay phenomenon, and accelerated proliferative retinopathy

A 42-year-old man with diabetes mellitus and probably acromegaly had a pituitary apoplexy with left-sided oculomotor palsy. There was an immediate fall in blood glucose concentration. Pituitary insufficiency promptly developed. Blood glucose levels remained normal for the next two years. During the first year after the pituitary apoplexy, severe proliferative retinopathy developed in the left eye, which became almost blind. Only mild retinopathy was present on the right side. Plasma concentrations of growth hormone remained low after the apoplexy, and the acromegalic features subsided. The explanation of these findings may be that the proliferative retinal angiopathy was caused by compression of the cavernous sinus at the time of the apoplexy. This would lead to impaired venous drainage, thus resembling occlusion of the central retinal vein, which may cause retinopathy similar to that seen in diabetes mellitus.

Glucose turnover rates in chronically catheterized non-pregnant and pregnant rabbits.

Glucose turnover rates have been measured in conscious, chronically catheterized, non-pregnant and pregnant rabbits. Non-pregnant rabbits were studied weekly for 4 wk. Pregnant animals were studied once while non-pregnant and then weekly for up to 4 wk during pregnancy. Glucose turnover rate was measured using a primed-constant infusion of [U-14C]glucose and [6-3H]glucose. The weight of the rabbits did not vary throughout the 4-5 wk of study in either the non-pregnant or pregnant group. Seven pregnant rabbits delivered pups which weighed an average of 61 g each. In non-pregnant rabbits, blood glucose concentration did not vary with time. In the pregnant rabbits, blood glucose concentration fell by the end of gestation to an average value of 74.6 +/- 2.7 mg/dl, significantly less (P less than 0.01) than the glucose concentration in the same animals before pregnancy, 88.2 +/- 2.4 mg/dl. The weight specific glucose turnover rate did not vary with time in either the non-pregnant (4.38 +/- 0.16 mg X min-1 X kg-1) or pregnant rabbits (3.89 +/- 0.29 mg X min-1 X kg-1). Blood glucose clearance did not change over time in the non-pregnant rabbits but did increase in the pregnant rabbits in late pregnancy. Blood glucose clearance was inversely related to the fall in blood glucose concentration.

The effect of diet on intermediary metabolite concentrations in Type 2 (non-insulin-dependent) diabetes mellitus.

The metabolic response to a standard meal was studied in six Type 2 (non-insulin-dependent) diabetic patients at diagnosis and following 4-6 weeks of dietary treatment. The fall in blood glucose concentration following treatment was accompanied by significant reductions in circulating concentrations of lactate, pyruvate, alanine and glycerol. Blood 3-hydroxybutyrate concentrations also fell with treatment.

Influence of hypoglucagonemia on splanchnic glucose output during leg exercise in man

Summary. The present study was undertaken to examine the role of glucagon in the regulation of hepatic glucose production during exercise. Using the hepatic vein catheter technique, the influence of somatostatin‐induced hypoglucagonemia on splanchnic exchange of glucose and glucose precursors during exercise was studied in normal postabsorptive man. In the experiments hypoglucagonemia was induced 10 min before and during 40 min of supine bicycle exercise (series 1), or 1–2 h before, and during, 40 min of upright bicycle exercise (series 2). The relative work intensities were 50% (series 1) and 55% (series 2) of maximal oxygen uptake. Control studies without somatostatin were conducted in both series.In both series, insulin and glucagon levels were suppressed by 40–50% throughout the period of somatostatin infusion. In series 1, somatostatin infusion at rest resulted in a 50 % fall in splanchnic glucose output. Onset of exercise during suppressed glucose production was followed by a rise in splanchnic glucose output similar to that seen in control subjects, but the absolute rate of glucose production was 5–25 % lower than in controls. In contrast to the euglycemia observed in the control experiment, exercise during somatostatin administration was accompanied by a 1–2 mmol/1 fall in blood glucose concentration due to the lower rate of glucose production.In series 2, a variable glucose infusion was added to the somatostatin administration before exercise to maintain euglycemia. After 1–2 h of somatostatin administration, glucose infusion was no longer required to prevent hypoglycemia, and splanchnic glucose output had returned to the basal level. At this time exercise was started. Both the rise in splanchnic glucose production and the absolute rate of splanchnic glucose output during exercise were similar to those observed without somatostatin. However, exercise during prolonged somatostatin infusion was accompanied by a gradual 50% rise in arterial glucose concentration, whereas no change in blood glucose during exercise was seen in controls.

Role of Liver in Glucose Homeostasis

The liver has a unique role in regulation of blood glucose in the postabsorptive state, after ingestion of glucose-containing meals, and in circumstances of glucopenia. It is soley responsible for the delivery of glucose to the bloodstream in the fasted state, thereby maintaining blood glucose concentration for the ongoing needs of body tissues, particularly the brain. An equally important role is played by the liver in the maintenance of normal glucose tolerance in response to carbohydrate ingestion. The liver is the principal site of glucose deposition after glucose feeding, while muscle and adipose tissue represent relatively minor sites of disposal of ingested glucose. In addition, the rise in glucose and insulin caused by glucose ingestion inhibits endogenous hepatic glucose production, which serves to minimize postprandial elevations in blood glucose. When blood glucose is reduced by small increments in circulating insulin, a rebound increase in glucose output from the liver is the initial or principal mechanism counteracting the fall in blood glucose concentration. Studies in juvenile-onset diabetes indicate that the liver is capable of altering its release of glucose in response to changes in blood glucose concentration when small, physiologic doses of insulin are infused. These findings may provide an explanation for the efficacy of preprogrammed insulin delivery systems in the treatment of diabetes.

The effect of chain length on glucose absorption and the related metabolic response

The relative absorption of saccharides of different chain length has been reexamined. Whether glucose is administered as a monosaccharide, a disaccharide (maltose), an intermediate polysaccharide mixture with a mean chain length of five glucose units (Caloreen), or a polysaccharide (starch), the rate of rise and fall in blood glucose concentration is similar in healthy subjects. In a maturity onset diabetic, peak blood glucose is similar whether monosaccharide or Caloreen is ingested. Plasma insulin and plasma free fatty acid responses to glucose saccharide ingestion do not appear to be affected by chain length. The dietary form in which starch is administered, rather than chain length, is probably important.

Effects of insulin and streptozotocin-induced diabetes on brain tryptophan and serotonin metabolism in rats.

Abstract—Previous work by other authors has shown hat insulin administration increases brain tryptophan levels and serotonin (5–HT) metabolism. The present study partially replicates these results and tests whether these effects could be due to insulin‐induced hypoglycemic stress, since stressers such as immobilization or food deprivation also increase brain tryptophan and 5‐HT metabolism. Ingestion of a dextrose solution by rats administered insulin (2 I.U./kg) prevents the extreme fall in blood glucose concentration and rise in plasma corticosterone following insulin injections alone. This treatment, however, produces a larger increase in brain tryptophan (30%) than insulin‐injected rats allowed only tap water. The greater accumulation of brain tryptophan may reflect an additive effect of the endogenously released insulin to that exogenously administered, since ingestion of the dextrose solution could trigger insulin secretion. In addition, brain tryptophan and 5‐HT metabolism were measured in streptozotocin‐diabetic rats maintained on several different feeding schedules to control for the effects of hyperphagia. All groups of diabetics showed significant decreases of approx 30% in brain tryptophan concentrations, while 5‐HT metabolism was unchanged. This deficit in brain tryptophan is reversed within 2 h after insulin administration (2 I.U./kg). These results indicate that changes in brain tryptophan and 5‐HT metabolism following insulin injections are not due to hypoglycemic stress, and that brain tryptophan is low in diabetics but increases above normal after administration of insulin. The results are discussed with respect to the effects of insulin on plasma levels of the neutral amino acids and a possible direct effect of insulin on the uptake of tryptophan by brain.

STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY

ABSTRACT Two patients with congenital generalized lipodystrophy have been studied at rest, and during and after long-term exercise at different carefully measured work loads. The two patients represented different stages of diabetes development. Both patients derived most of their energy used during muscular exercise from carbohydrate, and comparatively little from fat. FFA levels remained low throughout the period of observation in contrast to normal individuals and patients with juvenile diabetes. The data presented seem to show that deposition of glucose and free fatty acids (FFA) as triglyceride, must be impaired and are not compatible with the concept of increased triglyceride turnover in the adipocytes. The fall in blood glucose concentration (BCG) was less than in normal individuals and juvenile diabetics during exercise, and the glucose tolerance remained unchanged following work stop in both patients (k-values unchanged), in contrast to normal persons and patients with juvenile diabetes. Both patients showed significant falls in circulating immuno-reactive insulin (IRI) levels during exercise irrespective of a rise or fall in BGC. Thus, the exercise itself might activate endogenous mechanisms which could, on the one hand increase the circulating BGC, and at the same time force circulating IRI to decrease, thus disturbing the well-known relationship between circulating glucose and IRI levels as has been exhibited in normal subjects. The high IRI levels, also during exercise in these patients, indicate a' relative insulin resistance in the muscles, but less marked than the insulin resistance in the adipose tissue. The IRI response after glucose infusion did not change significantly with increasing work loads with one exception. Exercise did not alter significantly the human growth hormone (HGH) levels in either the diabetic or the non-diabetic patient indicating an abnormal regulation of the HGH secretion in congenital lipodystrophy.

The effect of acetoacetate on plasma insulin concentration.

1. Sodium acetoacetate was infused into the inferior vena cava of fed rats, 48h-starved rats, and fed streptozotocin-diabetic rats treated with insulin. Arterial blood was obtained from a femoral artery catheter. 2. Acetoacetate infusion caused a fall in blood glucose concentration in fed rats from 6.16 to 5.11mm in 1h, whereas no change occurred in starved or fed-diabetic rats. 3. Plasma free fatty acids decreased within 10min, from 0.82 to 0.64mequiv./l in fed rats, 1.16 to 0.79mequiv./l in starved rats and 0.83 to 0.65mequiv./l in fed-diabetic rats. 4. At 10min the plasma concentration rose from 20 to 49.9muunits/ml in fed unanaesthetized rats and from 6.4 to 18.5muunits/ml in starved rats. There was no change in insulin concentration in the diabetic rats. 5. Nembutal-anaesthetized fed rats had a more marked increase in plasma insulin concentration, from 30 to 101muunits/ml within 10min. 6. A fall in blood glucose concentration in fed rats and a decrease in free fatty acids in both fed and starved rats is to be expected as a consequence of the increase in plasma insulin. 7. The fall in the concentration of free fatty acids in diabetic rats may be due to a direct effect of ketone bodies on adipose tissue. A similar effect on free fatty acids could also be operative in normal fed or starved rats.

The role of glucose in insulin-induced feeding and drinking☆

The greater the dose of insulin given in a single injection the deeper the induced hypoglycaemia, whereas over the same dose range the amount of eating elicited comes to a maximum and then declines. The maximum rate of insulin-induced drinking occurs during rapid fall in blood glucose concentration but the induced eating coincides with a period of relatively constant blood glucose concentration. Injection of concentrated glucose with the insulin delays the induction of feeding, but co-injection of approximately isotonic glucose gives shorter feeding latencies than co-injection of more dilute solutions. Glucose ingestion at the time of insulin injection, but not before or after, eliminates induced feeding. Gastric intubation of glucose can block both eating and drinking responses to insulin. Unmetabolizable 3-methylglucose is not so effective at blocking the eating. Glycerol diminishes and intragastric palmitate augments the induced feeding. It is suggested that elicitation of eating by injected insulin is mediated by metabolic signals generated by adaptation to changed body glucose distribution.

EXPERIMENTAL LEUCINE-INDUCED HYPOGLYCEMIA IN MICE.

Administration of leucine to normal miceproduced a fall in blood glucose concentration, which was significantly augmented in mice pretreated with ultralente insulin. The ability of leucine to produce hypoglycemia following insulin pretreatment was not associated with decreased activity of either hepatic glucose-6-phosphatase or fructose-1, 6-diphosphatase. Leucine did significantly decrease in vivo incorporation of glycine-1-C 14 , pyruvate-2-C 14 , and glycerol-2-C 14 into glucose, but increased in vivo incorporation of glycerol-2-C 14 into hepatic lipid. It is suggested that leucine may produce hypoglycemia by inhibition of the formation of hepatic glucose.

The effect of insulin and tolbutamide on the reduced glutathione concentration in the blood of diabetic and non-diabetic persons.

Blood reduced glutathione (GSH) concentrations were determined in nondiabetic and mildly diabetic persons before and for 2 hr. after the injection of insulin or tolbutamide. The mean fall in blood glucose concentration caused by insulin was, for each group of persons, of about the same speed and magnitude as that following tolbutamide. The tolbutamide‐induced fall in glycmemia was accompanied by a significant and sustained percentage lowering of the mean blood GSH level in both groups of subjects: the insulin‐induced reduction in glyæsmia was unaccompanied by a sustained or significant percentage change in the blood GSH. Tolbutamide altered neither the glucose nor the GSH levels in the blood of an insulin‐dependent diabetic. The significance of these findings is discussed in relation to the mechanism of hypoglycaemic action of tolbutamide.

Effect of glucagon on peripheral utilization of glucose in man.

GLUCAGON (HGF) is known to produce hyperglycemia by stimulating hepatic glycogenolysis (1, 2, 3). However, the influence of this substance on utilization of glucose by peripheral cells has not been clearly defined (4, 5). De Duve (4) has referred to glucagon as a “powerful insulin antagonist,” and has stated that in this regard glucagon is at least as effective as epinephrine. Pincus and Rutman (5) have demonstrated that glucagon can prevent the fall in blood glucose concentration following administration of small doses of insulin. Yet, in order for this protective effect to occur, the animal studied must have been well fed, and the glucagon must be given by repeated injection or continuous infusion. Evidence from other sources (6, 7) also indicates that the hyperglycemic effect of infused glucagon is evanescent and that any effect glucagon might have on peripheral glucose utilization necessarily must be transient in nature as well.

CHANGES IN BLOOD GLUCOSE LEVELS AFTER HYPOTHALAMIC LESIONS

1. Section of the efferent hypothalamic pathways to the brain stem produces a fall in resting blood glucose level of about 38 per cent below that of normal rats kept under the same experimental conditions.2. Injection of a standard dose of insulin produced after 30 minutes the same fall in blood glucose concentration in rats with hypothalamic lesions as in normal animals.