A Mathematical Model for the Glucose Induced Insulin Release in Man

Abstract. The dynamics of the insulin response to intravenously administered glucose were studied in man. It was shown that (a) insulin response to prolonged stimulation is biphasic; (b) if the glucose stimulus is repeated with short intervals, inhibition of the second response occurs; (c) if longer time-intervals are used, enhancement of the response is noted at the second stimulation. These findings suggest that when the pancreatic islets are exposed to hyperglycaemia, three, kinetically distinct phenomena are initiated. Glucose induces almost instantaneous initiation of insulin release. Shortly thereafter, the pancreas enters a refractory phase. Thirdly, and at a later stage, a state of potentiation is built up in the islets. The effect of glucose on insulin synthesis is not considered here.–Against this background, and based on an earlier model, a mathematical model for the analysis of the glucose-insulin interplay during glucose infusions was constructed. The model describes the eventual occurrence of glucosuria, changes in the concentration of glucose in its pool, and mimics the effects of regulatory hormones when hypoglycemia appears. Insulin secretion is assumed to be con trolled, in a multiplicative manner, by an immediate glucose function, a hypothetical potentiator that is slowly generated by glucose, and a negative factor with a shorter time-course which corresponds to the refractory phase of the pancreas. A three compartment model is used in the simulation of the metabolism and distribution of insulin after its release. Finally, glucose utilization is described as a multiplicative function, related to the prevailing concentrations of glucose in blood and insulin in the extracellular space.–This model is able to simulate all the experimental situations described in this report, both in normal man and in the diabetic syndrome, in which insulin secretion shows varying degrees of impairment. The results of the simulation of individual experiments are given either as a set of theoretical parameter values, or described as the insulin response of the model to a standard, hypothetical glucose stimulus. The latter alternative is an attractive method for objectively evaluating the insulin response to a standard glucose load in clinical materials.     

Epinephrine-induced Insulin Resistance in Man

Endogenous release of epinephrine after stress as well as exogenous epinephrine infusion are known to result in impaired glucose tolerance. Previous studies of man and animals have demonstrated that this effect of epinephrine results from inhibition of insulin secretion and augmentation of hepatic glucose production. However, the effect of epinephrine on tissue sensitivity to insulin, and the relative contributions of peripheral vs. hepatic resistance to impaired insulin action, have not been defined. Nine young normal-weight subjects were studied with the insulin clamp technique. Plasma insulin was raised by ~100 μU/ml while plasma glucose concentration was maintained at basal levels by a variable glucose infusion. Under these conditions of euglycemia, the amount of glucose metabolized equals the glucose infusion rate and is a measure of tissue sensitivity to insulin. Subjects received four studies: (a) insulin (42.6 mU/m²·min), (b) insulin plus epinephrine (0.05 μg/kg·min), (c) insulin plus epinephrine plus propranolol (1.43 μg/kg·min), and (d) insulin plus propranolol. During insulin administration alone, glucose metabolism averaged 5.49±0.58 mg/kg·min. When epinephrine was infused with insulin, glucose metabolism fell by 41% to 3.26 mg/kg·min (P < 0.001). After insulin alone, hepatic glucose production declined by 92% to 0.16±0.08 mg/kg·min. Addition of epinephrine was associated with a delayed and incomplete suppression of glucose production (P < 0.01) despite plasma insulin levels >100 μU/ml. When propranolol was administered with epinephrine, total glucose metabolism was restored to control values and hepatic glucose production suppressed normally. Propranolol alone had no effect on insulin-mediated glucose metabolism. These results indicate that epinephrine, acting primarily through a β-adrenergic receptor, markedly impairs tissue sensitivity to an increase in plasma insulin levels, and that this effect results from both peripheral and hepatic resistance to the action of insulin.     

A Receptor Mechanism for the Inhibition Of Insulin Release by Epinephrine in Man

Normal adult men and women have been infused with epinephrine, 6 mug per minute, during lipolytic blockade with nicotinic acid, beta-adrenergic blockade with propranolol and Butoxamine, and alpha-adrenergic blockade with phentolamine. Epinephrine infusion was associated with low serum levels of immunoreactive insulin (IRI) except when phentolamine was given simultaneously. These findings are compatible with an alpha receptor mechanism for the epinephrine inhibition of insulin release. Phentolamine had no blocking effects on the tachycardia and widened pulse pressure or lipolytic stimulation by epinephrine, whereas both propranolol and Butoxamine blocked lipolysis, tachycardia, and widened pulse pressure. These findings are consistent with an alpha receptor blocking action for phentolamine and beta receptor blocking action for propranolol and Butoxamine. Inhibition of lipolysis by nicotinic acid did not alter IRI or glucose responses to epinephrine. It is concluded that the lipolytic effect of epinephrine is unrelated to its effects on IRI release. Lipolytic blockade by nicotinic acid also did not change IRI or glucose in fasting subjects or their responses to a glucose infusion, 300 mg per minute. These observations appear to conflict with the Randle hypothesis (the glucose-fatty acid cycle) and raise some doubt as to whether plasma FFA concentrations are direct determinants of glucose or IRI concentrations in normal man.     

Insulin Sensitivity of Forearm Tissues in Prediabetic Man

In genetic prediabetic subjects (the glucose tolerant offspring of two diabetic parents or the identical twin of a known diabetic) serum insulin concentrations after glucose administration are subnormal. Maintenance of glucose tolerance in this setting is apparently paradoxical, suggesting increased tissue insulin sensitivity. Accordingly, forearm tissue insulin sensitivity in nine genetic prediabetic males was compared with that of seven males without familial diabetes. Diabetes was excluded in all subjects by preliminary oral glucose tolerance testing.On the preliminary 3 h oral glucose tolerance test (OGTT) the sum of increments in blood glucose above fasting was greater in prediabetic than in control subjects. Conversely, the sum of increments in serum insulin was subnormal for the first 2 h. The insulin index (the sum of increments in insulin divided by the sum of increments in glucose) was significantly lower in prediabetics throughout the test. High physiologic levels of insulin were produced in the forearm by intrabrachial arterial insulin infusion (100 muU/kg per min for 26 min). Balances of glucose and amino acids across forearm muscle became more positive, as did balances of glucose and free fatty acids across adipose tissue plus skin. There were no differences in response between prediabetic and normal subjects.Hence, the insulin sensitivity of peripheral tissues is normal in genetic prediabetes. Increased tissue insulin sensitivity is not essential to explain coexisting euglycemia and insulinopenia in prediabetes because blood glucose values on the OGTT are, in fact, elevated although still within the range considered normal.     

Role of Insulin in the Regulation of Leucine Kinetics in the Conscious Dog

To study the effect of insulin on leucine kinetics, three groups of conscious dogs were studied after an overnight fast (16-18 h). One, saline-infused group (n = 5), served as control. The other two groups were infused with somatostatin and constant replacement amount of glucagon; one group (n = 6) received no insulin replacement, to produce acute insulin deficiency, and the other (n = 6) was constantly replaced with 600 muU/kg per min insulin, to produce twice basal hyperinsulinemia. Hepatic and extrahepatic splanchnic (gut) balance of leucine and alpha-ketoisocaproate (KIC) were calculated using the arteriovenous difference technique. l,4,5,[(3)H]Leucine was used to measure the rates (micromoles per kilogram per minute) of appearance (Ra) and disappearance (Rd), and clearance (Cl) of plasma leucine (milliliters per kilogram per minute).Saline infusion for 7 h resulted in isotopic steady state, where Ra and Rd were equal (3.2+/-0.2 mumol/kg per min). Acute insulin withdrawal of 4-h duration caused the plasma leucine to increase by 40% (P < 0.005). This change was caused by a decrease in the outflow of leucine (Cl) from the plasma, since Ra did not change. The net hepatic release of the amino acid (0.24+/-0.03 mumol/kg per min) did not change significantly; the arterio-deep femoral venous differences of leucine (-10+/-1 mumol/liter) and KIC (-12+/-2 mumol/liter) did not change significantly indicating net release of the amino and ketoacids across the hindlimb. Selective twice basal hyperinsulinemia resulted in a 36% drop in plasma leucine (from control levels of 128+/-8 to 82+/-7 mumol/liter, P < 0.005) within 4 h. This was accompanied by a 15% reduction in Ra and a 56% rise in clearance (P < 0.001, both). Net hepatic leucine production and net release of leucine and KIC across the hindlimb fell markedly. These studies indicate that physiologic changes in circulating insulin levels result in a differential dose-dependent effect on total body leucine metabolism in the intact animal. Acute insulin withdrawal exerts no effect on leucine rate of appearance, while at twice basal levels, insulin inhibited leucine rate of appearance and stimulated its rate of disappearance.     

The Adrenergic Modulation of the Serum Insulin Response to Intravenous Arginine in Man

Abstract. The effect of adrenergic stimulation and blockade on metabolic responses to arginine have been studied. Phentolamine enhanced, and adrenalin diminished, the rise in serum immunoreactive insulin that followed intravenous arginine; these effects were not secondary to changes in blood levels of arginine, glucose or free fatty acids following the amino acid infusion. Phentolamine did not affect the clearance of infused insulin from the blood stream. It was concluded that adrenergic receptor sites are involved in the modulation of the secretion of insulin in response to an infusion of arginine.     

3α-Androstanediol Kinetics in Man

Kinetics of 5alpha-androstane-3alpha, 17beta-diol (3alpha-diol) were studied in man. Clearance rates were determined by both the constant infusion and single injection techniques. Production rates were calculated as the product of clearance rate data and plasma values in the a.m. obtained by a radioimmunoassay specific for 3alpha-diol. Mean metabolic clearance rates were 1,776+/-492 (SD) liters/day in males and 1,297+/-219 (SD) liters/day in females. Metabolic clearance rates by single injection were similar. Calculated production rates are 208+/-26 (SD) mug/day in males and 35+/-11 mug/day in females, which are significantly different. Hepatic extraction of 3alpha-diol determined by hepatic vein catheterization during constant infusion was 76% which was greater than expected from information on in vitro binding in plasma. The kinetic data is of interest since 3alpha-diol has a calculated inner pool (V(1)) volume of 12-14 liters, similar to 17beta-hydroxyandrost-4-en-3-one (testosterone) and 5alpha-androstan-17beta-ol-3-one (dihydrotestosterone), but the calculated outer pool (V(2)) of 33.5 liters is very large as are the metabolic rate and transfer constant. In contrast to testosterone and dihydrotestosterone, 3alpha-diol, although bound to sex hormone binding globulin, has a high metabolic clearance of which a large fraction represents extrahepatic (splanchnic) metabolism. A production rate of 3alpha-diol similar to dihydrotestosterone together with rather unique kinetic characteristics encourages further investigation of the biological role of this potent androgen.     

The Effect of Gastrin on Basal- and Glucose-Stimulated Insulin Secretion in Man

The effect of gastrin on basal- and glucose-stimulated insulin secretion was studied in 32 normal, young subjects. The concentration of gastrin and insulin in serum was measured radioimmunochemically.Maximal physiologic limit for the concentration of gastrin in serum was of the order of 160 pmol per liter as observed during a protein-rich meal. Oral ingestion of 50 g glucose produced a small gastrin response from 28+/-3 to 39+/-5 pmol per liter (mean +/-SEM, P < 0.01).Intravenous injection or prolonged infusion of gastrin increased the concentration of insulin in peripheral venous blood to a maximum within 2 min followed by a decline to basal levels after a further 10 min. The minimum dose required to induce a significant insulin response (31.2 ng gastrin per kg) increased the gastrin level in serum above the physiologic range. Maximum effect was obtained with 500 ng gastrin per kg.When 15.6 ng (7.1 pmol) gastrin per kg body weight and 25 g glucose were injected simultaneously, the glucose-induced insulin response was potentiated (from 2.32+/-0.33 to 4.33+/-0.98 nmol per liter per 20 min, P < 0.02), even though gastrin concentrations only increased to 71.2+/-6.6 pmol per liter. No effect, however, was noted on glucose disposal. 15.6 ng gastrin per kg given i.v. 30 min before an i.v. glucose tolerance test was without significant effect on the insulin response.The results indicate that gastrin can stimulate a rapid and short-lived release of insulin. In physiologic concentrations gastrin potentiates the glucose-stimulated insulin secretion and is without effect on basal insulin secretion. A small release of gastrin during oral glucose ingestion may to a limited extent contribute to the nonglycemic insulin secretion. During protein ingestion, gastrin probably stimulates insulin secretion significantly.     

Simultaneous Measurement of Thyroxine and Triiodothyronine Peripheral Turnover Kinetics in Man

Serum triiodothyronine (T(3)) kinetics in man have been difficult to define presumably due to the interference of iodoproteins generated during the peripheral metabolism of T(3). The use, in the present study, of an anion-column chromatographic method for separation of serum T(3) as well as thyroxine (T(4)) from these iodoproteins has overcome this technical handicap. Simultaneous measurement of serum (125)I-T(3) and (131)I-T(4) kinetics were performed in 31 subjects from the clinical categories of euthyroid, primary hypothyroid, thyrotoxic and posttreatment hypothyroid Graves' disease, factitial thyrotoxic, and idiopathically high and low thyroxinebinding globulin states. The normal mean T(3) fractional turnover rate (kT(3)) was 0.68 (half-life = 1.0 days), increased in toxic Graves' disease patients to 1.10 (half-life = 0.63 days), and decreased in primary hypothyroid patients to 0.50 (half-life = 1.38 days). The mean T(3) equilibration time averaged 22 hr except in hypothyroid and high thyroxine-binding globulin (TBG) patients where the equilibration period was delayed by 10 hr. The mean T(3) distribution space in normal subjects was 38.4 liters. This was reduced in subjects with high TBG levels (26 liters) and increased in patients with low TBG and in all hyperthyroid states (53-55 liters). The normal serum T(3) concentration was estimated by radioimmunoassay to be 0.106 mug/100 ml. Combined with the mean T(3) clearance value of 26.1 liters/day, the calculated T(3) production rate was 27.6 mug/day. The mean T(3) production rate increased to 201 mug/day in thyrotoxic Graves' disease patients and was reduced to 7.6 mug/day in primary hypothyroid subjects. T(3) production rate was normal in subjects with altered TBG states. The ratio of T(3) to T(4) production rate in normal subjects was 0.31 and was unchanged in patients with altered TBG values. This ratio was increased in all Graves' disease patients with the highest value being 0.81 in the posttreatment hypothyroid Graves' disease group. This apparent preferential production of T(3) may have been responsible for the retention of rapid turnover kinetics for T(3) and T(4) observed in treated Graves' disease patients. The finding that factitial thyrotoxic patients also displayed similar rapid T(3) and T(4) turnover kinetics indicates that these alterations are not a unique feature of Graves' disease per se. When comparing the peripheral turnover values for T(3) and T(4) in man, it is apparent that alterations in metabolic status and serum TBG concentration influence both hormones in a parallel manner; however, changes in metabolic status seem to have a greater influence on T(3) kinetics while alterations in TBG concentrations have a greater effect on T(4). These observations probably relate to the differences in TBG binding affinity and peripheral tissue distribution of these two hormones.     

Teaching and Learning the Trinity-Unity Model of Man

A method by which the trinity-unity model of personhood might be integrated within a pre-existing medical school curriculum is presented. Preparatory literature, brief lectures, and small group work are used in a modular, problem-solving way gradually to familiarize students with the concepts necessary for both 'medicine of persons' and 'medicine of bodies'. Concrete and fluid thought patterns, the trinity-unity model of personhood, language games, and hierarchical systems analysis are all essential elements.     

Influence of Endogenous Insulin Secretion on Splanchnic Glucose and Amino Acid Metabolism in Man

Splanchnic exchange of glucose, 20 individual amino acids, lactate, and pyruvate was studied in normal subjects in the postabsorptive state and after stimulation of endogenous insulin secretion by infusion of glucose at two dose levels. In the basal state, mean splanchnic glucose production was 3.4 mg/kg per min. A net uptake of lactate, pyruvate, and nine amino acids was observed, with alanine accounting for half of the total splanchnic-amino acid extraction.Infusion of glucose at 25 mg/kg per min for 20 min resulted in a fivefold increase in arterial insulin levels and in reversal of splanchnic glucose balance to a net uptake. Splanchnic uptake of alanine, glycine, phenylalanine, lactate, and pyruvate fell by 30-60% due to a reduction in fractional extraction of these substrates, inasmuch as their arterial concentrations did not decline.Administration of glucose at 2 mg/kg per min for 45 min resulted in a 19 mg/100 ml increase in arterial glucose concentration and a doubling of arterial insulin levels. Despite the small increment in insulin, hepatic glucose production fell by 85%. Splanchnic exchange of amino acids, lactate, and pyruvate was unaltered. Estimated total glucose utilization during the infusion was no greater than in the basal state, indicating lack of stimulation of peripheral glucose uptake.IT IS CONCLUDED THAT: (a) inhibition of hepatic glucose production associated with glucose infusion and large increments in insulin levels occurs in the absence of a decrease in the concentration of circulating gluconeogenic substrate, suggesting an hepatic rather than peripheral effect; (b) the liver is the primary target organ whereby glucose homeostasis is achieved with small increments in insulin; (c) the relatively greater sensitivity of the liver's response to insulin as compared with an effect of insulin on the peripheral tissues, may be a consequence of the higher levels of endogenous insulin in portal as compared with peripheral blood.     

Changes in Insulin Immunoreactivity across the Coronary Circulation in Man during Infusions of Glucose and a Fat Emulsion

Abstract. The extraction of immunoreactive insulin by the human heart has been examined using the technique of coronary sinus catheterisation. The subjects were 12 male volunteers. During the study infusions of a fat emulsion and glucose were given in an effort to create a "steady fed state". The higher arterial insulin immunoreactivities which were observed during the infusions were associated with greater arterial coronary sinus differences in insulin immunoreactivity. The possibility of insulin degradation by the heart is discussed. During prolonged exercise the process of insulin removal by the heart appeared more active.     

Effect of Lipids on Insulin,Growth Hormone and Exocrine Pancreatic Secretion in Man *

Abstract. Influences of fat on release of insulin, growth hormone and pancreatic enzyme secretion were studied in 35 metabolically healthy subjects. A fat solution containing 40 g of soy bean oil was administered, I. V., orally and intraduodenally. In all cases there was a similar increase of insulin but the rise in serum insulin after oral or intraduodenal fat administration was not related to the changes in plasma free fatty acids, free glycerol and triglyceride levels. Blood sugar responded according to insulin secretion. The route of fat administration may possibly influence growth hormone secretion. Following intraduodenal fat administration volume and bicarbonate contents of the duodenal juice rose slightly whereas trypsin and bilirubin content increased considerably. These results suggest that insulin secretion after oral or intraduodenal administration of fat is influenced by intestinal factors. Cholecystokinin-pancreozymin and gastric inhibitory polypeptide are qualified to serve as such factors.     

实验性胰岛素抵抗综合征大鼠模型

目的:建立胰岛素抵抗综合征大鼠模型.方法:用高脂高糖高盐饲料喂养大鼠八周,观察大鼠饮水量,体重,血压,葡萄糖耐量,血脂,血糖及血胰岛素水平,并算出胰岛素敏感性指数等.结果:与基础饲料组大鼠相比,高脂高糖高盐饲料组大鼠饮水量明显增多(多出47%,P＜0.01);体重明显增加(高出11%,P＜0.01);血压明显升高(高出20%,P＜0.01);葡萄糖耐量明显降低(P＜0.01);血清甘油三酯和胆固醇均明显增高(分别高出49%和57%,二者均P＜0.01);高密度脂蛋白胆固醇明显降低(低出30%,P＜0.05);血糖和胰岛素均明显升高(分别高出12%,P＜0.05和69%,P＜0.01),胰岛素敏感性指数明显降低(P＜0.01).结论:高脂高糖高盐饮食可以造成胰岛素抵抗综合征大鼠模型.     

Metabolism of Very Low Density Lipoproteins in Hyperlipidaemia: Studies of Apolipoprotein B Kinetics in Man

The metabolism of very low density lipoprotein-B (VLDL-B) peptide was studied in nineteen subjects with endogenous hypertrigylceridaemia (Types V, IV and lib), three patients with heterozygous familial hyperbetalipoproteinaemia (Type Ila) and eight healthy subjects, by reinjecting autologous radioiodinated VLDL. The kinetics of VLDL-B peptide were followed. The mean turnover rate of VLDL-B peptide was significantly higher in the hypertriglyceridaemic group than in the control group but a considerable overlap in turnover rate was found between these groups. The patients with heterozygous familial hyperbetalipoproteinaemia had a normal turnover rate of VLDL-B peptide. A significant positive correlation was found between the turnover rate of VLDL-B peptide and VLDL-triglyceride concentration in the whole series. It is concluded that the underlying defect in endogenous hypertriglyceridaemia is heterogeneous. Overproduction of VLDL is a major determining factor in seme patients whereas a reduced clearance is the determining factor in others.     

实验性NIDDM模型胰岛素抵抗的评估

目的：用糖耐量曲线下面积（SBG）、胰岛素释放曲线下面积（SIns)、胰岛素敏感素敏感指数,这些临床糖尿病常用的指标对非胰岛素依赖性糖尿病（noninsulin-dependent diabetes melitus,NIDDM)模型胰岛素抵抗评估。方法：大鼠永主射小剂量链尿佐菌素,使大鼠糖耐量异常 ,然后加喂高热量食物,引起动物肥胖,饲养8wk,可形成类似NIDDM的肥胖大鼠模型,并设置对照组,同时测定了大鼠糖耐量试验过程中血清葡萄糖（BG）、胰岛素（Ins),并计算了SBG、SIns、胰岛素敏感指数,结果：①模型组糖耐量试验,血清BG糖耐量下降,Ins在糖负荷后2h明显升高（P＜0．01）;②Ins敏感指数较对照组明显降低（P＜0．01）;③SBG明显上升（P＜0．01）;SIns无明显变化,SIns／SBG下降（P＜0．01）。结论SBG、SIns胰岛素敏感指数可较好反映Ins作用,B细胞储备功能及Ins敏感性,可广泛用于实验性糖尿闰作作为临床正确评价IR的指标。     

Differential Effects of Insulin on Splanchnic and Peripheral Glucose Disposal after an Intravenous Glucose Load in Man

The present study was designed to investigate the mechanisms by which insulin regulates the disposal of an intravenous glucose load in man. A combined tracer-hepatic vein catheter technique was used to quantitate directly the components of net splanchnic glucose balance (NSGB), i.e., splanchnic glucose uptake and hepatic glucose output, and peripheral (extrasplanchnic) glucose uptake. Four different protocols were performed: (a) intravenous infusion of glucose alone (6.5 mg kg⁻¹ min⁻¹) for 90 min (control group); (b) glucose plus somatostatin (0.6 mg/h) and glucagon (0.8 ng kg⁻¹ min⁻¹; (c) glucose plus somatostatin, glucagon, and insulin (0.15 mU kg⁻¹ min⁻¹); and (d) glucose plus somatostatin, glucagon, and insulin (0.4 m U kg⁻¹ min⁻¹). In groups 2-4, arterial blood glucose was raised to comparable levels to those of controls (170 mg/dl) by a variable glucose infusion. In the control group, plasma insulin levels reached 40 μU/ml at 90 min. NSGB switched from a net output of 1.71±0.13 to a net uptake of 1.5-1.6 mg kg⁻¹ min⁻¹ due to a 90-95% suppression of hepatic glucose output (P < 0.01) and a 105-130% elevation of splanchnic glucose uptake (from 0.78±0.13 to 1.6-1.8 mg kg⁻¹ min⁻¹; P < 0.01). Peripheral glucose uptake rose by 150-160% (P < 0.01). In group 2, plasma insulin fell to <5 μU/ml. Net splanchnic glucose output initially rose twofold but later returned to basal values. This response was entirely accounted for by similar changes in hepatic glucose output since splanchnic glucose uptake remained totally unchanged in spite of hyperglycemia. In contrast, peripheral glucose uptake rose consistently by 100% (P < 0.01) despite insulin deficiency. In an additional group of experiments, glucose metabolism by the forearm muscle tissue was quantitated during identical conditions to those of group 2 (hyperglycemia plus insulin deficiency). Both the arterial-deep venous blood glucose difference and forearm glucose uptake increased markedly by 300-400% (P < 0.05 - <0.01). In group 3, plasma insulin was maintained at near-basal, peripheral levels (12-14 μU/ml). Hepatic glucose output decreased slightly by 35-40% (P < 0.05) while splanchnic glucose uptake remained unchanged. Consequently, the net glucose overproduction seen in group 2 was totally prevented although NSGB still remained as a net output. In group 4, peripheral insulin levels were similar to those of the control group (35-40 μU/ml). The suppression of hepatic glucose output was more pronounced (60-65%) and splanchnic glucose uptake rose consistently by 65% (P < 0.01). Consequently, NSGB did not remain as a net output but eventually switched to a small uptake (0.3 mg kg⁻¹ min⁻¹). Peripheral glucose uptake rose to the same extent as in controls.     

The Glucose-Induced Gastrointestinal Stimulation of Insulin Secretion in Man: Relation to Age and to Gastrin Release

Abstract. An oral 50 g glucose tolerance test and a simple intravenous glucose infusion test were performed in 20 young (20–32 years), 20 middle-aged (42–55 years), and 20 old (65–81 years) normal subjects. Blood glucose, serum insulin, and serum gastrin concentrations were measured during all tests. The intravenous glucose infusion duplicated the oral blood glucose curve in young, middle-aged, and half of the old subjects. In the remaining old subjects the intravenous blood glucose curve was below the oral blood glucose curve. Glucose and insulin concentrations were of similar magnitude in all groups, but maximum concentrations were reached later in the old subjects. Glucose per os induced a rapid rise in serum gastrin concentrations of the order of 10 pmol/1 and a subsequent decrease of about 20 pmol/1 in all groups. The intravenous glucose infusion induced no significant changes in serum gastrin concentrations. The non-glycaemic (i. e. enteral) stimulation of insulin secretion was expressed as the difference between the integrated incremental areas of the oral and intravenous insulin curves in subjects with identical glucose curves during the two tests. This stimulation was of similar magnitude in all age groups, and it was not correlated to variations in gastrin concentrations. However, in the young subjects the enteral stimulation was greater during the first 30 minutes and smaller during the two last hours when compared to the old subjects.
The results suggest that: 1. A simple intravenous glucose infusion test can be used to copy the oral blood glucose curve. 2. The size of the enteral stimulation of insulin secretion during the whole test is independent of age. 3. The action of the glucose-induced enteral stimulation is delayed with age, and closely linked to the dynamics of the glycaemic stimulus. 4. The glucose-induced gastrin release is probably too small to affect insulin secretion significantly.