Estimation of insulin secretion using extracts of plasma from mice injected with anti-insulin serum: effects of arginine, glucose and anti-insulin serum

1982 ◽  
Vol 95 (1) ◽  
pp. 125-135
Author(s):  
L. V. Beck ◽  
Ilora Basu ◽  
Sally L. Hegeman
Keyword(s):  
Insulin Secretion ◽  
Plasma Insulin ◽  
Plasma Sample ◽  
Fixed Time ◽  
Endogenous Insulin ◽  
Insulin In Plasma ◽  
Plasma Insulin Levels ◽  
Time Required ◽  
Secretion Rates

Anti-insulin serum (AIS) injected intravenously into adult male mice was allowed to complex endogenous plasma insulin for a fixed time before blood samples were taken. In each plasma sample, insulin was separated from antibody using acid alcohol and the free insulin was estimated by radioimmunoassay. We consider AIS to be most useful for the estimations of in-vivo insulin secretion rates over the period 0·5–5 min after its injection. The lower limit is governed by the time required for mixing and complexing of endogenous insulin. The use of a short upper limit is because antibody complexed with antigen leaves plasma more rapidly than does free antibody, carrying antigen with it. Increases in insulin per ml plasma were appreciably greater in mice injected with glucose or l-arginine plus AIS than in mice injected with glucose or l-arginine only. Hence more realistic values for in-vivo insulin secretion rates may be obtained by the use of AIS to retain most insulin in plasma than by estimations of plasma insulin levels.

Pulsatile insulin secretion accounts for 70% of total insulin secretion during fasting

1995 ◽  
Vol 269 (3) ◽  
pp. E478-E488 ◽  
Author(s):  
N. Porksen ◽  
S. Munn ◽  
J. Steers ◽  
S. Vore ◽  
J. Veldhuis ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Portal Vein ◽  
Basal Insulin ◽  
Deconvolution Analysis ◽  
Insulin Secretion In Vivo ◽  
Endogenous Insulin Secretion ◽  
Endogenous Insulin ◽  
Basal Insulin Secretion ◽  
Secretion Rates

The purpose of the present study was to determine the contributions of discrete insulin secretory bursts vs. basal insulin release to total insulin secretion in vivo. Quantification of the partitioning of pulsatile and basal insulin secretion is complicated by physiological delivery of these pulses into the portal vein and the absence of validated methods of measuring the rates of pulsatile and basal insulin secretion in vivo. We therefore 1) developed a canine model with chronically implanted portal vein catheters, 2) validated an established deconvolution technique as well as a novel direct catheterization technique (Clustcath) for measurement of pulsatile and nonpulsatile insulin secretion rates in this model, and 3) applied these methods to study insulin secretion in the overnight-fasted dog in vivo to determine the contribution of pulsatile vs. basal insulin secretion to total rates of endogenous insulin secretion. Rates of total, pulsatile, and nonpulsatile endogenous insulin secretion measured by Cluscath closely parallel those measured by deconvolution analysis (54 +/- 15 vs. 51 +/- 11, 38 +/- 12 vs. 36 +/- 11, and 16 +/- 4 vs. 14 +/- 4 pmol/min, respectively). Clustcath and deconvolution indicated that the majority of insulin was secreted as pulses (70 +/- 6 and 66 +/- 7%, respectively). These data infer that any process that selectively decreases the pulsatile component of insulin secretion (e.g., diabetes mellitus) will likely have a major impact on total insulin secretion.

Mechanisms of acute hyperinsulinemia after Kupffer cell phagocytosis

1980 ◽  
Vol 238 (3) ◽  
pp. E276-E283 ◽  
Author(s):  
R. P. Cornell
Keyword(s):  
Insulin Secretion ◽  
Kupffer Cells ◽  
Plasma Insulin ◽  
Insulin Receptors ◽  
Insulin Levels ◽  
Peripheral Plasma ◽  
Pancreatic Insulin ◽  
Plasma Insulin Levels ◽  
Hepatic Insulin Extraction

Blockade of hepatic Kupffer cells by prior phagocytosis of a variety of particulate materials caused acute hyperinsulinemia in glucose-stimulated fasted rats under pentobarbital anesthesia. At 4-h postblockade a 125-250% increase in peripheral plasma insulin levels occurred due to a combination of enhanced pancreatic insulin secretion and depressed hepatic insulin extraction. Enhanced pancreatic insulin secretion was confirmed by a 36-54% elevation of portal venous insulin levels. Depressed hepatic insulin extraction was indicated by a 37-47% reduction in insulin uptake by in situ perfused livers as well as alterations in portal-hepatic venous insulin differences and intravenous insulin tolerance tests in vivo. All parameters began to return toward control values at 24 and 48 h postblockade. Return was slow after inert carbon phagocytosis and rapid after degradable bacteria phagocytosis. Peripheral plasma insulin levels were very highly correlated with glucose clearance rates in all groups both control and experimental. Mechanisms are proposed to explain these findings based on the release of lysosomal enzymes and endogenous pyrogens by phagocytizing Kupffer cells as well as the presence of insulin receptors on hepatocytes and Kupffer cells.

Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

1988 ◽  
Vol 255 (6) ◽  
pp. R1035-R1040
Author(s):  
R. Hoo-Paris ◽  
M. L. Jourdan ◽  
L. C. Wang ◽  
R. Rajotte
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Low Temperatures ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Exogenous Insulin ◽  
Metabolic Substrate ◽  
Endogenous Insulin ◽  
Dose Dependent Decrease ◽  
Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

scholarly journals Cephalic phase insulin secretion is KATP channel independent

2013 ◽  
Vol 218 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Yusuke Seino ◽  
Takashi Miki ◽  
Wakako Fujimoto ◽  
Eun Young Lee ◽  
Yoshihisa Takahashi ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Critical Role ◽  
Pancreas Perfusion ◽  
Glucose Levels ◽  
Cephalic Phase ◽  
Plasma Insulin Levels ◽  
Atropine Methyl Nitrate ◽  
Nutrient Injection

Glucose-induced insulin secretion from pancreatic β-cells critically depends on the activity of ATP-sensitive K+channels (KATPchannel). We previously generated mice lackingKir6.2, the pore subunit of the β-cell KATPchannel (Kir6.2−/−), that show almost no insulin secretion in response to glucosein vitro. In this study, we compared insulin secretion by voluntary feeding (self-motivated, oral nutrient ingestion) and by forced feeding (intra-gastric nutrient injection via gavage) in wild-type (Kir6.2+/+) andKir6.2−/−mice. Underad libitumfeeding or during voluntary feeding of standard chow, blood glucose levels and plasma insulin levels were similar inKir6.2+/+andKir6.2−/−mice. By voluntary feeding of carbohydrate alone, insulin secretion was induced significantly inKir6.2−/−mice but was markedly attenuated compared with that inKir6.2+/+mice. On forced feeding of standard chow or carbohydrate alone, the insulin secretory response was markedly impaired or completely absent inKir6.2−/−mice. Pretreatment with a muscarine receptor antagonist, atropine methyl nitrate, which does not cross the blood–brain barrier, almost completely blocked insulin secretion induced by voluntary feeding of standard chow or carbohydrate inKir6.2−/−mice. Substantial glucose-induced insulin secretion was induced in the pancreas perfusion study ofKir6.2−/−mice only in the presence of carbamylcholine. These results suggest that a KATPchannel-independent mechanism mediated by the vagal nerve plays a critical role in insulin secretion in response to nutrientsin vivo.

ANF inhibits glucose-stimulated insulin secretion in mouse and rat

1988 ◽  
Vol 255 (5) ◽  
pp. E579-E582 ◽  
Author(s):  
B. Ahren
Keyword(s):  
Insulin Secretion ◽  
Atrial Natriuretic Factor ◽  
Plasma Insulin ◽  
Glucagon Secretion ◽  
Insulin Levels ◽  
Atrial Cells ◽  
Insulin And Glucagon Secretion ◽  
Plasma Insulin Levels ◽  
Glucose Stimulated Insulin Secretion ◽  
Dose Levels

Atrial natriuretic factor (ANF) is synthesized in atrial cells and was recently demonstrated to also occur within islet glucagon cells. Therefore, we investigated the possible effects of synthetic rat ANF-(1-28) on basal and stimulated insulin and glucagon secretion in the mouse and on glucose-induced insulin secretion in the rat. We found that ANF did not affect basal levels of insulin, glucagon, or glucose when injected intravenously at dose levels between 0.25 and 4.0 nmol/kg in mice. However, when injected together with glucose (2.8 mmol/kg), ANF (4.0 nmol/kg) inhibited the increase in plasma insulin levels by 40%, from 114 +/- 8 microU/ml in controls to 81 +/- 8 microU/ml (P less than 0.01). Likewise, the increase in plasma insulin levels during an intravenous infusion of glucose in rats (10 mg/min) was significantly reduced by ANF (100 pmol.kg-1.min-1; P less than 0.001). In contrast, the increase in plasma levels of insulin and glucagon after the intravenous injection of the cholinergic agonist carbachol in mice (0.16 mumol/kg) was not significantly affected by ANF. We conclude that ANF inhibits glucose-stimulated insulin secretion in the mouse and the rat. The peptide may therefore be a modulator of insulin secretion.

Effect of gestational hyperglycemia on insulin secretion in vivo and in vitro by fetal rat pancreas

1986 ◽  
Vol 251 (1) ◽  
pp. E86-E91 ◽  
Author(s):  
M. T. Bihoreau ◽  
A. Ktorza ◽  
A. Kervran ◽  
L. Picon
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
Insulin Release ◽  
Plasma Insulin ◽  
Cell Function ◽  
Pregnant Rats ◽  
Fetal Rat ◽  
Gestational Hyperglycemia

The effects of gestational hyperglycemia on B-cell function were studied in near-term fetuses from unrestrained pregnant rats made slightly or highly hyperglycemic using continuous glucose infusion during the last week of pregnancy. Pancreatic and plasma insulin and insulin secretion in vitro were studied in the fetuses. Compared with controls, slightly hyperglycemic fetuses showed increased pancreatic and plasma insulin concentrations and similar insulin release in response to glucose in vitro. In highly hyperglycemic fetuses, pancreatic and plasma insulin concentrations were unchanged compared with controls, and insulin release in vitro was insensitive to glucose and to the mixture glucose plus theophylline. These results confirm that glucose is able to stimulate insulin secretion in normal or slightly hyperglycemic fetuses and suggest that severe hyperglycemia per se, without association of other metabolic disorders or toxic injuries, profoundly alters the stimulus-secretion coupling of the fetal rat B-cell.

Sensitivity of insulin secretion to feedback inhibition by hyperinsulinaemia

1981 ◽  
Vol 98 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Ralph A. DeFronzo ◽  
Christian Binder ◽  
John Wahren ◽  
Philip Felig ◽  
Eleuterio Ferrannini ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Feedback Inhibition ◽  
Normal Subjects ◽  
Insulin Concentration ◽  
Plasma Insulin Concentration ◽  
C Peptide ◽  
Endogenous Insulin ◽  
Arterial Plasma

Abstract. The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an intravenous infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg/min for two hours. Arterial plasma insulin concentration achieved during the infusion segregated into three levels of hyperinsulinaemia: 35 ± 1 (mean ± sem), 87 ± 15 and 828 ± 210 μU/ml. Plasma glucose concentration was kept constant at the basal level by a variable glucose infusion. Fasting C-peptide (0.29 ± 0.02 pmol/ml) fell significantly in all subjects during hyperinsulinaemia and reached a concentration of 0.19 ± 0.03 pmol/ml at 60 min and 0.14 ± 0.03 at 120 min after the start of the insulin infusion. The C-peptide response was not related to the infusion dose nor to the steady state plasma insulin concentration. It is concluded that (a) basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24 ± 3 μU/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and (b) supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinaemia.

ENHANCEMENT OF INSULIN RELEASE TO ACUTE GLYCAEMIC STIMULATION WITH DEPRESSION OF BASAL INSULIN PRODUCTION RATES IN INSULINOMA FOLLOWING DIAZOXIDE ADMINISTRATION

1970 ◽  
Vol 63 (3) ◽  
pp. 392-404 ◽  
Author(s):  
Richard E. Bailey ◽  
Albert Castro ◽  
Rosanne M. Kramer ◽  
Dorothy Macfarlane
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Release ◽  
Plasma Insulin ◽  
Insulin Biosynthesis ◽  
Oral Glucose ◽  
Glucose Tolerance Tests ◽  
Tolerance Curve ◽  
Insulinoma Cells ◽  
Secretion Rates

ABSTRACT Single and double load oral glucose tolerance tests were performed repetitively both before and during administration of diazoxide to a 15-year old girl who had an insulin secreting islet cell tumour. Plasma insulin concentrations increased above baseline values by a greater magnitude in response to a single acute oral glycaemic stimulus following diazoxide treatment, compared to the increases resulting from comparable prediazoxide glucose tolerance tests, and plasma insulin either attained higher values or sustained elevations for a longer duration during the early part (first hour) of the single load tests. This provides evidence that diazoxide does not prevent the normal insulin release response to a glycaemic stimulus, and that enhanced insulin secretion rates may occur with insulinomas under the study conditions employed. Fasting plasma insulin concentrations were lower during the period of diazoxide administration which indicates that insulin biosynthesis was depressed under fasting steady-state conditions. Considering that the first part of the glucose tolerance curve reflects primarily insulin release, our data is consistent with the view that insulin storage within the insulinoma cells is preserved under the study conditions employed and may even be enhanced by diazoxide. Consequently, depression of insulin biosynthesis is considered to be a resultant effect and not a primary action of diazoxide. These results suggest a possible basis for »distinguishing« types of insulinomas should additional perspective reveal that glycaemic-induced enhancement of insulin secretion rates cannot be made to occur uniformly in diazoxide treated patients having insulinomas.

A NEW PRINCIPLE FOR THE COMPARISON OF INSULIN SECRETORY RESPONSES

1973 ◽  
Vol 74 (3) ◽  
pp. 511-523 ◽  
Author(s):  
Klaus Johansen
Keyword(s):  
Blood Glucose ◽  
Plasma Insulin ◽  
Intravenous Glucose ◽  
Endogenous Insulin ◽  
Glucose Ratio ◽  
Insulin Secretagogues ◽  
Plasma Insulin Levels ◽  
Young Subjects ◽  
Insulin Secretory Response ◽  
Selection Of

ABSTRACT A new principle for the comparison of insulin secretory response has been devised. It consists in the selection of groups of subjects with identical glucose tolerance when subjected to the same amount of oral and intravenous glucose and of intravenous tolbutamide. In this way the problems and assumptions inherent in the use of the insulin/glucose ratio and the administration of different amount of insulin secretagogues have been avoided. Using this new method of comparison of insulin secretory responses it has been demonstrated that young people maintain the same blood glucose level after stimulation with much smaller plasma insulin levels than their older counterparts, i. e. young non-diabetic and diabetic subjects seem to be more 'sensitive' to endogenous insulin than the old, alternately the old subjects are more 'resistant' to endogenous insulin than young subjects.

Pancreatic insulin response in relation to exercise training

1983 ◽  
Vol 61 (10) ◽  
pp. 1194-1197 ◽  
Author(s):  
Denis Richard ◽  
Jacques LeBlanc
Keyword(s):  
Exercise Training ◽  
Plasma Insulin ◽  
Direct Evidence ◽  
Insulin Response ◽  
Exercise Bout ◽  
Female Rats ◽  
Pancreatic Insulin ◽  
Plasma Insulin Levels ◽  
Plasma Insulin Response

The present study was undertaken to measure the effects of exercise training on pancreatic insulin secretion in response to glucose and nonglucose stimuli. Wistar female rats with an initial body weight of approximately 180 g were divided into trained and sedentary groups. After a period of 10 weeks of training, glucose-, tolbutamide-, and arginine-tolerance tests were performed in vivo in both trained and untrained animals. The tests were done in nonanesthetized animals 40 h after the last exercise bout. It was found that exercise training leads to a diminution of plasma insulin levels after either glucose, tolbutamide, or arginine administration. These results present direct evidence that exercise training reduces plasma insulin response not only to glucose but also to nonglucidic secretagogues.

Sign in / Sign up

Export Citation Format

Share Document