A Relationship Between the Blood Sugar Level and the Rate of Sugar Utilization, Affecting the Theories of Diabetes

Soskin, Samuel; Levine, Rachmiel

doi:10.1152/ajplegacy.1937.120.4.761

Cited by 115 publications

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“…The glucose infusion experiments indicate that peripheral utilization of glucose is proportional to arterial glucose levels in the range between 80 and 210 mg. per cent in agreement with previous work (16)(17)(18). Glucagon results in significantly greater glucose utilization at comparably elevated glucose levels.…”

Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

“…(The average difference between duplicate determinations was 2 per cent.) The antecubital vein carries venous drainage from the deep and superficial tissues of the forearm (13-15), while capillary blood has the same glucose content as arterial blood (16)(17)(18).Sodium space was determined in 8 subjects receiving glucagon and 12 subjects receiving glucose alone using radiosodium (Na') which was added to the infusion fluid. Plasma samples (drawn along with samples for glucose determination) were assayed for radioactivity in a R-C Scientific scintillation well type counter.…”

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confidence: 99%

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The Enhancement of Peripheral Glucose Utilization by Glucagon

Elrick¹,

Hlad²,

Witten³

et al. 1955

J. Clin. Invest.

113

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During the past 30 years evidence has been accumulating which suggests that glucagon (the hyperglycemic-glycogenolytic factor of the pancreas) is a true hormone and that it is produced in the Islets of Langerhans (1, 2). Its purification and crystallization were finally accomplished in 1953 by Staub, Sinn, and Behrens (3). The crystalline material is a simple protein with a molecular weight of approximately 4,200 and an amino acid composition which differs in important ways from that of insulin (4). This establishes glucagon as an entity distinct from insulin.Crystalline glucagon is an extremely active substance. In the cat, 0.05 y per Kg. body weight causes a significant rise in blood sugar which lasts 25 minutes (4). Sutherland, Cori, Wosilait, and Rall (5, 6) have shown that glucagon stimulates the synthesis of active phosphorylase in the liver. This enzyme catalyzes the rate-limiting reaction (glycogen ;± glucose-i-phosphate) in the transformation of glycogen to glucose. The effect of glucagon on liver phosphorylase adequately explains its well-known hyperglycemic-glycogenolytic action.With respect to its role in carbohydrate metabolism, some investigators look upon glucagon as an insulin antagonist (1, 2, 7) while others consider it an insulin synergist (8, 9). Still others are skeptical of its hormonal nature (10,11 per min. in different subjects) by means of a constant infusion pump (Bowman) for periods of 120 to 145 minutes. In 12 subjects glucagon2 (0.7 to 1.0 mg.) was added to the perfusate following an initial period of 40 to 60 minutes with glucose alone. In 12 subjects the glucose infusion rate was doubled after 50 minutes and after 90 minutes the initial rate was resumed in order to simulate the hyperglycemia caused by glucagon. Two subjects received glucose at a constant rate for 2 hours. The initial control data on 8 other subjects who subsequently received other hormones were also used in the analysis of data.Glucose determinations (Nelson-Somogyi Method) (12) were done on venous (indwelling needle in antecubital vein) and capillary (finger) blood from the same arm at 5 or 10-minute intervals, using 0.2-ml. samples (30 to 40 samples from each subject). Venous samples were drawn without stasis and analyzed in duplicate. (The average difference between duplicate determinations was 2 per cent.) The antecubital vein carries venous drainage from the deep and superficial tissues of the forearm (13-15), while capillary blood has the same glucose content as arterial blood (16)(17)(18).Sodium space was determined in 8 subjects receiving glucagon and 12 subjects receiving glucose alone using radiosodium (Na') which was added to the infusion fluid. Plasma samples (drawn along with samples for glucose determination) were assayed for radioactivity in a R-C Scientific scintillation well type counter. The method used to calculate sodium space by this technique will be described elsewhere (19

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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The Enhancement of Peripheral Glucose Utilization by Glucagon

Elrick¹,

Hlad²,

Witten³

et al. 1955

J. Clin. Invest.

113

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“…This is an important question since it has been suggested that in normal man as much as half of the decline in plasma glucose concentration following glucose administration is due to the mass action effect of hyperglycaemia [10]. Soskin and Levine in 1937 were the first to study the relationship between the blood glucose level and glucose utilization in pancreatectomized diabetic dogs and suggested that hyperglycaemia provided a compensatory mechanism to maintain normal rates of tissue glucose uptake in the presence of insulin deficiency [11]. We, as well as others, have demonstrated that in both NIDDM and IDDM individuals hyperglycaemia serves a compensatory role to offset the insulin resistance and maintain a normal rate of insulin-mediated glucose disposal [7,8,[12][13][14][15].…”

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confidence: 99%

Studies on the mass action effect of glucose in NIDDM and IDDM: evidence for glucose resistance

et al. 1997

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Tissue glucose uptake occurs via a facilitated transport system [1]. The major factors that regulate glucose uptake in vivo are the prevailing plasma glucose and insulin concentrations. Following glucose ingestion the plasma glucose concentration rises, insulin secretion is stimulated and the combination of hyperglycaemia and hyperinsulinaemia contributes to the increase in glucose utilization. Plasma glucose concentration influences glucose utilization by a mass Diabetologia (1997) Summary The ability of hyperglycaemia to enhance glucose uptake was evaluated in 9 non-insulin-dependent (NIDDM), 7 insulin-dependent (IDDM) diabetic subjects, and in 6 young and 9 older normal volunteers. Following overnight insulin-induced euglycaemia, a sequential three-step hyperglycaemic clamp (+ 2.8 + 5.6, and + 11.2 mmol/l above baseline) was performed with somatostatin plus replacing doses of basal insulin and glucagon, 3-3 H-glucose infusion and indirect calorimetry. In the control subjects as a whole, glucose disposal increased at each hyperglycaemic step (13.1 ± 0.6, 15.7 ± 0.7, and 26.3 ± 1.1 m mol/kg ⋅ min). In NIDDM (10.5 ± 0.2, 12.1 ± 1.0, and 17.5 ± 1.1 m mol/kg ⋅ min), and IDDM (11.2 ± 0.8, 12.9 ± 1.0, and 15.6 ± 1.1 m mol/kg ⋅ min) glucose disposal was lower during all three steps (p < 0.05-0.005). Hepatic glucose production declined proportionally to plasma glucose concentration to a similar extent in all four groups of patients. In control subjects, hyperglycaemia stimulated glucose oxidation (+ 4.4 ± 0.7 m mol/kg ⋅ min) only at + 11.2 mmol/l (p < 0.05), while non-oxidative glucose metabolism increased at each hyperglycaemic step (+ 3.1 ± 0.7; + 3.5 ± 0.9, and + 10.8 ± 1.7 m mol/kg ⋅ min; all p < 0.05). In diabetic patients, no increment in glucose oxidation was elicited even at the highest hyperglycaemic plateau (IDDM = + 0.5 ± 1.5; NIDDM = + 0.2 ± 0.6 m mol/kg ⋅ min) and non-oxidative glucose metabolism was hampered (IDDM = + 1.8 ± 1.5, + 3.1 ± 1.7, and + 4.3 ± 1.8; NIDDM = + 0.7 ± 0.6, 2.1 ± 0.9, and + 7.0 ± 0.8 m mol/kg ⋅ min; p < 0.05-0.005). Blood lactate concentration increased and plasma non-esterified fatty acid (NEFA) fell in control (p < 0.05) but not in diabetic subjects. The increments in blood lactate were correlated with the increase in non-oxidative glucose disposal and with the decrease in plasma NEFA. In conclusion: 1) the ability of hyperglycaemia to promote glucose disposal is impaired in NIDDM and IDDM; 2) stimulation of glucose oxidation and non-oxidative glucose metabolism accounts for glucose disposal; 3) both pathways of glucose metabolism are impaired in diabetic patients; 4) impaired ability of hyperglycaemia to suppress plasma NEFA is present in these patients. These results suggest that glucose resistance, that is the ability of glucose itself to promote glucose utilization, is impaired in both IDDM and NIDDM patients. [Diabetologia (1997) 40: 687-697] Keywords Hyperglycaemia, mass action effect, glucose-mediated glucose metabolism, glucose oxidation, non-oxidative glucose metabol...

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“…This speculation has been given additional weight by the demonstration that anterior pituitary growth hormone, a well established diabetogenic agent, causes release of a glucagonlike substance from the pancreas of experimental animals (5). The present investigation was undertaken to discover whether glucagon could produce an elevated blood glucose concentration with inhibition of glucose utilization, since this combination is usually observed in diabetic patients (9)(10)(11). These studies confirm and extend previous observations (12) that glucagon does not interfere with the uptake of glucose by the peripheral tissues.…”

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The Effect of Glucagon on Carbohydrate Metabolism in Normal Human Beings 1

Bondy¹,

Cardillo²

1956

J. Clin. Invest.

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Since the isolation of glucagon (hyperglycemicglycogenolytic factor, HGF) from the pancreas (1, 2), and the demonstration that it is released in appreciable amounts into the blood stream (3)(4)(5), there has been much speculation about the possibility that diabetes mellitus may result from an imbalance between secretion of insulin and glucagon (6)(7)(8). This speculation has been given additional weight by the demonstration that anterior pituitary growth hormone, a well established diabetogenic agent, causes release of a glucagonlike substance from the pancreas of experimental animals (5). The present investigation was undertaken to discover whether glucagon could produce an elevated blood glucose concentration with inhibition of glucose utilization, since this combination is usually observed in diabetic patients (9)(10)(11) Alpha amino nitrogen content of plasma and whole blood was determined on venous samples according to the method of Frame, Russell, and Wilhelmi (16,17).The concentration of blood ketone bodies was determined on arterial samples by a modification (18) of the method of Greenberg and Lester (19).In acute experiments, three control pairs of arteriovenous samples were drawn and then 1.0 ml. (0.95 mg.) of glucagon3 was immediately injected through the venous Cournand needle. Samples were taken 1, 2, 3, 5, 7, 10, and 15 minutes after the injection. A control experiment was run in two cases, by repeating the entire procedure, substituting a slow intravenous drip of 5 per cent glucose in water for glucagon. The rate of administration of glucose was adjusted to produce an arterial glucose curve approximating that produced by glucagon. The control experiments followed the glucagon experiments by at least one week.The effect of HGF on the peripheral circulation was studied by following skin temperatures and finger plethysmographs in two volunteers for fifteen minutes after the injection of glucagon. The subjects rested in a constant temperature room at 82 degrees F. for twentyfour minutes before the inj ections. Skin temperatures were measured in seven locations by thermocouples; relative blood flow was estimated by finger plethysmography, using the technique of Burch (20). No blood chemical determinations were made in these subjects.In a second group of subjects, 0.04 mg. per Kg. of glucagon was administered in 240 to 300 ml. of 0.9 per cent saline intravenously at a constant rate over the course of two hours. Control arterial and venous samples were drawn five minutes before and at the start of the glucagon infusion, and 15, 30, 60, and 120 minutes thereafter, while the glucagon was being administered. In 3 The glucagon preparation employed in these experiments, kindly supplied by Dr 494

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A Relationship Between the Blood Sugar Level and the Rate of Sugar Utilization, Affecting the Theories of Diabetes

Cited by 115 publications

References 0 publications

The Enhancement of Peripheral Glucose Utilization by Glucagon

The Enhancement of Peripheral Glucose Utilization by Glucagon

Studies on the mass action effect of glucose in NIDDM and IDDM: evidence for glucose resistance

The Effect of Glucagon on Carbohydrate Metabolism in Normal Human Beings 1

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