Effects of intraduodenal nutrient infusion on insulin response to subsequent intravenous glucose in rats

Abstract Insulin resistance (IR) engenders a compensatory increase in plasma insulin. Inadequate compensation is a primary element in the pathogenesis of Type 2 diabetes. The signal which heralds developing IR and initiates hyperinsulinemic compensation is not known. It has often been assumed to be increased glucose. We tested this assumption by determining whether development of fasting and/or glucose-stimulated hyperinsulinemia with diet-induced insulin resistance occurs because of concomitant elevation of glycemia. Male dogs (n=58) were fed a hypercaloric, fat-supplemented diet for 6 wks. Dogs underwent MRI to quantify total and regional (visceral, subcutaneous) adiposity as well as euglycemic hyperinsulinemic clamps. A subset of animals also underwent an insulin-modified intravenous glucose tolerance test (IVGTT) to assess insulin sensitivity, acute insulin response (AIRg), and glucose effectiveness. Fat feeding caused modest weight gain, increased visceral and subcutaneous fat, and IR at both peripheral and hepatic levels. Hyperinsulinemic compensation was observed in fasting levels as well as increased AIRg. However, we observed absolutely no increase in carefully measured fasting, evening (6-8 pm) or nocturnal glycemia (2-4 am). IR and hyperinsulinemia occurred despite no elevation in 24-hour glucose. Compensatory development of hyperinsulinemia during diet-induced insulin resistance occurs without elevated fasting or 24-hour glycemia. These data refute the idea that glucose itself is a requisite signal for β-cell upregulation. Alternative feedback mechanisms need to be identified.

Download Full-text

Interactions of cold exposure and starvation on glucose tolerance and insulin response

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.245.6.e575 ◽

1983 ◽

Vol 245 (6) ◽

pp. E575-E581 ◽

Cited By ~ 3

Author(s):

A. L. Vallerand ◽

J. Lupien ◽

L. J. Bukowiecki

Keyword(s):

Glucose Tolerance ◽

Cold Acclimation ◽

Cold Exposure ◽

Plasma Insulin ◽

Insulin Response ◽

Insulinogenic Index ◽

Intravenous Glucose ◽

Peripheral Tissues ◽

Insulin Levels ◽

Plasma Insulin Levels

The metabolic interactions of cold exposure, cold acclimation, and starvation on glucose tolerance and plasma insulin levels were studied in precannulated, unrestrained, and unanesthetized rats. Cold exposure (48 h at 5 degrees C) significantly reduced the insulin response to intravenous glucose injection (P less than 0.01) while improving glucose tolerance (P less than 0.01). Starvation (48 h at 25 degrees C) also reduced the insulin response (P less than 0.01) but did not significantly alter glucose tolerance. “Accelerated starvation” induced by starving rats for 48 h at 5 degrees C dramatically reduced both basal and glucose-stimulated insulin levels while even improving glucose tolerance, resulting in a 15-fold reduction in the insulinogenic index. Cold acclimation (3 wk at 5 degrees C) induced essentially the same alterations as cold exposure. Approximately reversed changes were observed when cold-acclimated rats were returned to a warm environment for 15–18 h. Results from these studies indicate that 1) cold exposure and starvation, but not cold acclimation, act synergistically in decreasing the sensitivity and/or the capacity of pancreatic islets for secreting insulin in response to glucose stimulation; 2) glucose tolerance and possibly insulin sensitivity of peripheral tissues are enhanced by cold exposure and starvation, although glucose tolerance is improved by cold exposure only, not by starvation; 3) an improved glucose tolerance with barely detectable plasma insulin levels was obtained in cold-starved rats under normal physiological conditions.

Download Full-text

Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.275.6.e1031 ◽

1998 ◽

Vol 275 (6) ◽

pp. E1031-E1036 ◽

Cited By ~ 7

Author(s):

Claudio Cobelli ◽

Francesca Bettini ◽

Andrea Caumo ◽

Michael J. Quon

Keyword(s):

Glucose Tolerance ◽

Minimal Model ◽

Insulin Response ◽

Model Analysis ◽

Published Data ◽

Glucose Kinetics ◽

Model Estimate ◽

Intravenous Glucose ◽

Glucose Effectiveness ◽

Model Independent

Glucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890–896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model-independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns.

Download Full-text

Gestational diabetes reverses the circadian variation of plasma insulin response to intravenous glucose

American Journal of Obstetrics and Gynecology ◽

10.1016/s0002-9378(88)80018-8 ◽

1988 ◽

Vol 159 (3) ◽

pp. 607-611

Author(s):

Alexander D. Kofinas ◽

Paul J. Meis ◽

James C. Rose

Keyword(s):

Gestational Diabetes ◽

Plasma Insulin ◽

Circadian Variation ◽

Insulin Response ◽

Intravenous Glucose ◽

Plasma Insulin Response

Download Full-text

FURTHER STUDIES ON HEALTHY SUBJECTS WITH LOW AND HIGH INSULIN RESPONSE TO GLUCOSE INFUSION

Acta Endocrinologica ◽

10.1530/acta.0.0550305 ◽

1967 ◽

Vol 55 (2) ◽

pp. 305-329 ◽

Cited By ~ 37

Author(s):

Erol Cerasi ◽

Rolf Luft

Keyword(s):

Healthy Subjects ◽

Insulin Response ◽

Glucose Infusion ◽

Oral Glucose ◽

Intravenous Glucose ◽

The Family ◽

High Insulin ◽

History Of ◽

Insulin Response To Glucose ◽

Plasma Insulin Response

ABSTRACT In a previous paper it was shown that 15 out of 85 healthy subjects with a normal intravenous glucose tolerance demonstrated a low plasma insulin response to glucose infusion which was similar to that obtained in diabetic subjects. In the present paper it has been shown that the type of insulin response to glucose infusion was the same when the test was repeated. Low insulin responders to glucose infusion, as a group, also showed low insulin response to intravenous tolbutamide and oral glucose. This indicates that the type of insulin response is characteristic for a given subject irrespective of the stimulation used. There seemed to be no difference in the occurrence of diabetes in the family history of the groups of low and high insulin responders.

Download Full-text

Modified protocols improve insulin sensitivity estimation using the minimal model

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.253.6.e595 ◽

1987 ◽

Vol 253 (6) ◽

pp. E595-E602 ◽

Cited By ~ 22

Author(s):

Y. J. Yang ◽

J. H. Youn ◽

R. N. Bergman

Keyword(s):

Standard Deviation ◽

Insulin Sensitivity ◽

Minimal Model ◽

Insulin Response ◽

Tolerance Test ◽

Intravenous Glucose Tolerance Test ◽

Improve Insulin Sensitivity ◽

Intravenous Glucose ◽

Sensitivity Estimation ◽

Model Technique

We attempted to improve the precision of the estimation of insulin sensitivity (S1) from the minimal model technique by modifying insulin dynamics during a frequently sampled intravenous glucose tolerance test (FSIGT). Tolbutamide and somatostatin (SRIF) were used to change the insulin dynamics without directly affecting insulin sensitivity. Injection of tolbutamide (100 mg) at t = 20 min provoked an immediate secondary peak in insulin response, resulting in a greater integrated incremental insulin than the standard FSIGT. SRIF, injected at t = -1 min, delayed insulin secretion in proportion to the dose without any change in magnitude. Computer simulation was used to assess the precision of S1 estimation. Insulin dynamics from both standard and modified protocols were adjusted in magnitude, with the shape unchanged and analyzed to determine the effect of the magnitude of insulin response. Fractional standard deviation was reduced from 73% with the standard insulin profile to 23% with tolbutamide and 18% with the highest dose of SRIF. In addition, the fractional standard deviation of S1 estimates decreased exponentially with increasing magnitude of insulin response. Modified FSIGTs require a smaller insulin response than the standard protocol to achieve the same precision.

Download Full-text