Effects of truncated glucagon-like peptide-1 on pancreatic hormone release in normal conscious dogs

1990 ◽  
Vol 123 (6) ◽  
pp. 661-667 ◽  
Author(s):  
Koichi Kawai ◽  
Seiji Suzuki ◽  
Shinichi Ohashi ◽  
Hidehito Mukai ◽  
Yasuko Murayma ◽  
...  
Keyword(s):  
Glucose Level ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Plasma Glucose Level ◽  
Insulin Level ◽  
Glucose Infusion ◽  
Plasma Insulin Level ◽  
Plasma Glucagon ◽  
Glucagon Level ◽  
Glucagon Like Peptide 1

Abstract. The effects of truncated glucagon-like peptide-1 (GLP-1) on insulin and glucagon release were examined in unanesthetized normal dogs. A bolus injection of GLP-1 (7-36)amide elicited a transient increase in the plasma insulin level, which brought about a decrease in the plasma glucose level. The degree of increase in plasma insulin levels with GLP-1 (7-35)OH or GLP-1 (7-37)OH was less than that induced by GLP-1 (7-36)amide. The plasma glucagon level did not increase in spite of mild hypoglycemia. The infusion of graded doses of GLP-1 (7-36)amide (6, 36, 120 ng · kg−1 · min−1 every 30 min) did not change the plasma glucose, insulin or glucagon levels significantly. The degree of increase in the plasma glucose level induced by iv glucose infusion (12 mg · kg−1 · min−1) was reduced by coinfusion of GLP-1(7-36)amide (6 ng · kg−1 · min−1), although the degree of increase in the plasma insulin level was the same as that in a control experiment (coinfusion of the vehicle). Coinfusion of GLP-1 (7-36)amide (60 ng · kg−1 · min−1) caused an augmented increase in the plasma insulin level and a reduced increase in the plasma glucose level during iv glucose infusion (17 mg · kg−1 · min−1) compared with the control experiment. The degree of decrease in the plasma glucagon level during iv glucose infusion was not affected by the coinfusion. The degree of increase in the plasma glucagon level induced by insulin hypoglycemia and the profile of the plasma glucose level at that time were not affected by the infusion of GLP-1 (7-36)amide. These results demonstrate that 1. the insulinotropic activity of GLP-1 (7-36)amide is higher than that of GLP-1(7-37)OH or GLP-1(7-35)OH; 2. GLP-1 (7-36)amide suppresses the degree of increase in plasma glucose level during iv glucose infusion by augmented insulin release, and 3. the glucagonostatic activity of truncated GLP-1 is negligible under physiological conditions.

Assessment of insulin action in man: role of hyperglycemia

1988 ◽  
Vol 119 (2) ◽  
pp. 213-222 ◽  
Author(s):  
E. Martens ◽  
R. Zick ◽  
H. J. Mitzkat ◽  
A. von zur Mühlen ◽  
M. J. Müller
Keyword(s):  
Glucose Level ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Plasma Glucose Level ◽  
Insulin Level ◽  
Maximum Effect ◽  
Insulin Responsiveness ◽  
Sensitivity Data

Abstract. The effect of hyperglycemia on insulin-induced glucose metabolism (M) was investigated in healthy subjects using sequential clamp protocols at constant insulin + somatostatin infusions and varying plasma glucose. During euglycemia (4.8 mmol/l) M increased from 5.6 to 12.5 mg·kg−1·min−1 with increasing plasma insulin (0.34-3.00 nmol/l). At increasing glucose (6.7 mmol/l), M further increased (9.7 to 19.2 mg·kg−1·min−1) with the plasma insulin level (0.41 to 2.99 nmol/l). At a plasma glucose level of 9.8 mmol/l insulin (0.42 to 3.17 nmol/l) was still effective to increase M (13.7 to 25.2 mg·kg−1·min−1). Regression analysis showed that hyperglycemia does not only increase the maximal insulin-stimulated M, but also decreases the insulin concentration causing a half maximum effect. During prolonged clamp studies M increased by about 10% per h, independent by the plasma glucose level. We conclude that hyperglycemia increases M by increasing insulin responsiveness as well as insulin sensitivity. Data derived from euglycemic clamp studies alone are of limited value with respect to the assessment of insulin action.

Disappearance of insulin in man: variation with the plasma insulin level

1981 ◽  
Vol 97 (3) ◽  
pp. 391-397 ◽  
Author(s):  
Karl-Göran Tranberg ◽  
Per Hagander ◽  
Jan Thorell
Keyword(s):  
Clearance Rate ◽  
Pancreatic Secretion ◽  
Plasma Insulin ◽  
Insulin Level ◽  
Glucose Infusion ◽  
Plasma Insulin Level ◽  
Exogenous Insulin ◽  
Fasting State ◽  
Endogenous Insulin ◽  
Arterial Blood

Abstract. Clearance rates of unlabelled insulin were studied in 45 unanaesthetized non-diabetic humans. The clearance rate, as well as the pancreatic secretion rate, of endogenous insulin was estimated from steady-state concentrations in portal and arterial blood. The clearance rate of exogenous insulin was determined after brief intraportal infusion. In the basal fasting state, the endogenous plasma insulin level varied as closely with the clearance of endogenous insulin as with the rate of pancreatic secretion. During elevation of insulin by glucose infusion, it varied predominantly with the rate of insulin secretion. Clearance of exogenous insulin did not vary with the pre-test endogenous insulin level. The clearance of endogenous insulin increased from 11 ml · min−1 · kg−1 in the basal fasting state to 17 ml · min−1 · kg−1 during glucose infusion. Clearance of exogenous insulin fell progressively with increasing dose, from 35 (8 mU/kg) to 14 (43 mU/kg) ml · min−1 · kg−1 at normoglycaemia and from 23 (8 mU/kg) to 17 (34 mU/kg) ml · min−1 · kg−1 at hyperglycaemia. The clearance of endogenous insulin was lower than that of exogenous insulin at normoglycaemia, but of similar size during glucose infusion. It is concluded that variation in clearance rate is partly responsible for variation in plasma insulin concentration, particularly in the basal fasting state, and that the clearance rate is lower in the basal state than otherwise. To some extent, the low clearance values for endogenous insulin in the basal state may reflect poor specificity of the insulin radioimmunoassay.

scholarly journals OR26-07 Mild Physiologic Hyperglycemia Does Not Affect Glucose Mediated but Impairs Insulin-Mediated Suppression of Plasma Glucagon in Healthy Normal Glucose Tolerant Subjects

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Devjit Tripathy ◽  
Xi chen ◽  
aurora merovci ◽  
Jonathan Trejo ◽  
Ralph DeFronzo
Keyword(s):  
Plasma Glucose ◽  
Plasma Insulin ◽  
Glucose Infusion ◽  
Plasma Glucagon ◽  
Euglycemic Clamp ◽  
Hyperglycemic Clamp ◽  
Before And After ◽  
Normal Glucose ◽  
Glucose Tolerant ◽  
Plasma Insulin Levels

Abstract Plasma glucagon levels are regulated by plasma glucose concentrations as well as intra-islet and circulating insulin concentrations. Hyperglycemia adversely affects skeletal muscle and hepatic insulin sensitivity (glucotoxicity). However, the effect of physiologic hyperglycemia on glucose-mediated and insulin-mediated suppression of glucagon is not known. The aim of the present study was to evaluate effect of chronic (48 or 72 hours) physiologic increase (+45 mg/dl) in plasma glucose concentration on the suppression of plasma glucagon concentration in healthy NGT individuals: 12 without family history of T2DM (FH-) (9M/3F, age = 50± 4 yrs, BMI = 27 ± 1 kg/m2) and 8 with FH of T2DM (FH+) (4M/4F, age = 48±2, BMI = 26±1 kg/m2). Subjects received an OGTT and 2-step hyperglycemic (+125 and +300 mg/dl) clamp (duration of each step = 80 minutes) before and after 72 hour glucose infusion. On another occasion subjects participated in a 3-step hyperinsulinemic (10, 20, 40 mU/m2·min) euglycemic clamp before and after a 48 hour glucose infusion. Plasma insulin and C-peptide concentrations were obtained every 2-5 minutes during each hyperglycemic clamp step and plasma glucagon concentrations were measured every 10 minutes. The ratio of insulin/glucagon was measured and used as an index of insulin-medicated suppression of plasma glucagon. FPG concentration increased from 97±4 to 140±4 mg/dl during the 72 hour glucose infusion. Following chronic glucose infusion, plasma insulin levels were significantly higher during the basal state and during each hyperglycemic clamp step (by 59% and 78%). There was no difference in plasma glucagon levels following chronic glucose infusion and the degree of suppression of glucagon during 2-step hyperglycemic (+125 and +300 mg/dl) were similar. However, the plasma insulin/glucagon ratio was significantly higher during the fasting state (by 76%) and during the first (by 128%) and second (by 178%) hyperglycemic clamp steps. Similarly during the three step euglycemic clamp (10, 20, 40 mU/m2·min) studies following 48 hr glucose infusion, despite similar plasma glucose concentrations during each clamp step, plasma insulin and glucagon concentrations were higher following chronic glucose infusion. These results demonstrate that sustained physiologic hyperglycemia for 48 hrs or 72 hours (i.e. glucotoxicity) does not affect the glucose mediated suppression of glucagon, but impairs insulin-mediated suppression of glucagon, and could contribute to fasting and post-prandial hyperglycemia in T2DM patients.

Insulin-like effect of vanadyl ion on streptozotocin-induced diabetic rats

1990 ◽  
Vol 126 (3) ◽  
pp. 451-459 ◽  
Author(s):  
H. Sakurai ◽  
K. Tsuchiya ◽  
M. Nukatsuka ◽  
M. Sofue ◽  
J. Kawada
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Plasma Insulin ◽  
Active Form ◽  
Insulin Level ◽  
Plasma Insulin Level ◽  
High Concentration ◽  
Vanadyl Ion ◽  
Vanadyl Sulphate

ABSTRACT Recent studies have indicated that the blood glucose level of rats with streptozotocin (STZ)-induced diabetes (type 1) is normalized without an increase in the plasma insulin level by administration of sodium orthovanadate in the drinking water. The mechanism of this insulin-like effect of vanadate is unknown. In this study, we investigated whether vanadyl ion, which is less toxic than vanadate to rats, also has an insulin-like effect in rats with STZ-induced diabetes. When rats with STZ-induced diabetes were given a daily i.p. injection of vanadyl sulphate (9·3 and 4·6 mg vanadium/kg body weight), their blood glucose level decreased from about 22·2 to about 7·2 mmol glucose/l within 2 days and remained low for at least 12 weeks. This treatment did not affect their low plasma insulin level. Quantitative electron spin resonance (ESR) spectrometry showed that most of the vanadium (about 90%) in their tissues was present as a vanadyl form (VO2+). ESR analysis also showed that the vanadyl ion in tissues was bound endogenously with four oxygen ligands from either water or oxyamino acid residues in proteins. Vanadyl sulphate accelerated glucose incorporation into adipocytes of rats, suggesting that the action of vanadyl ion is peripheral. Interestingly, vanadyl sulphate at a high concentration (about 10 mmol/l) was more effective than insulin in enhancing glucose uptake. This study demonstrated that: (1) vanadyl sulphate (+ 4 oxidation state), like vanadate ion, normalizes the blood glucose levels of rats with STZ-induced diabetes; (2) the action of vanadyl ion is peripheral; and (3) the active form of vanadium for an insulin-like effect may be a vanadyl form, not vanadate. Journal of Endocrinology (1990) 126, 451–459

Validity of the operational equation of the 14C-deoxyglucose method modified for changing arterial plasma glucose level.

1987 ◽  
Vol 36 (2) ◽  
pp. 217-222
Author(s):  
Kortaro Tanaka ◽  
Fumio Gotoh ◽  
Shintaro Gomi ◽  
Shutaro Takashima ◽  
Ban Mihara
Keyword(s):  
Glucose Level ◽  
Plasma Glucose ◽  
Plasma Glucose Level ◽  
Operational Equation ◽  
Arterial Plasma ◽  
Deoxyglucose Method

scholarly journals Effect of clonidine on plasma insulin level in mice. Polia pharmacol

1978 ◽  
Vol 74 (3) ◽  
pp. 383-388
Author(s):  
Hikaru OZAWA ◽  
Masayoshi GOTO ◽  
Michiko TAKAHASHI ◽  
Toshio UEMATSU
Keyword(s):  
Plasma Insulin ◽  
Insulin Level ◽  
Plasma Insulin Level
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