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R N Bergman

Publications and source records attributed to R N Bergman.

177 records · Page 10Linked to original sources
PubMed1979

Quantitative estimation of insulin sensitivity.

We have evaluated the feasibility of using a mathematical model of glucose disappearance to estimate insulin sensitivity. Glucose was injected into conscious dogs at 100, 200, or 300 mg/kg. The measured time course of insulin was regarded as the "input," and the falling glucose concentration as the "output" of the physiological system storing and using glucose. Seven mathematical models of glucose uptake were compared to identify the representation most capable of simulating glucose disappearance. One specific nonlinear model was superior in that it 1) predicted the time course of glucose after glucose injection, 2) had four parameters that could be precisely estimated, and 3) described individual experiments with similar parameter values. Insulin sensitivity index (SI), defined as the dependence of fractional glucose disappearance on plasma insulin, was the ratio of two parameters of the chosen model and could be estimated with good reproducibility from the 300 mg/kg injection experiments (SI = 7.00 X 10(-4) +/- 24% (coefficient of variation) min-1/(microU/ml) (n = 8)). Thus, from a single glucose injection it is possible to obtain a quantitative index of insulin sensitivity that may have clinical applicability.

Animals↗
PubMed1978

Neurohypophyseal hormone-responsive renal adenylate cyclase. IV. A random-hit matrix model for coupline in a hormone-sensitive adenylate cyclase system.

A "random-hit" matrix model is proposed to account for the dynamic and steady state relationship between occupation of bovine renal medullary membrane receptors by [Lys8]vasopressin (LVP) and neurohypophyseal hormones (NHH) and the associated activation of membrane-bound adenylate cyclase. The model was developed by systematic introduction of specific rules concerning receptor coupling into a general structural model which consists of two square matrices of identical size, one composed of homogeneous R ("receptor") units, the second of homogeneous C ("cyclase") units. R units are either occupied (RO) or unoccupied (RU); C units are either active (CA) or inactive (CI). Hormone molecules are envisioned to "collide" with R units randomly; collision with RU leads to "binding", and occupation is maintained for a characteristic mean occupancy time, TO. In this structure, each R unit has an "interaction field" which consists of the "twin" unit in the "C" matrix, and the 4 nearest neighbor C units surrounding the twin. Occupation of an R unit leads to activation of all CI units in the interaction field of that R; CA units in the interaction field are refractory. Thus binding at a given R may "recruit" a variable number of inactive neighboring C units (5, 4, 3, 2, 1, or 0). The model requires that there be individual coupling delays between the moment of binding at a given R and subsequent activation of CI units (mean coupling delay (Td) approximately 10% To). Activation of C units persists as long as the "parent" R is occupied and is maintained for an additional short time interval (Tp) after RO reverts to RU, corresponding to hormone dissociation from receptor. The model accounts for the following previously demonstrated relations between LVP occupation of receptors and adenylate cyclase activation in bovine renal medullary membranes: 1) the shape of the nonlinear steady state relation between normalized (percentage maximal) receptor occupation (O) and cyclase activation (A), uniformly observed in different membrane preparations: 2) variable hormone concentration-dependent trajectories of approach to the final steady state A:O value (A:Oss) which may be either monophasic or biphasic; 3) the loss of intrinsic adenylate cyclase activity observed in bovine membranes for a series of NHH analogs with progressively diminishing affinity for receptors. The model represents an explicit theory of coupling where a successive series of temporal events are quantitatively related to each other and privide major constraints to any interpretation of the molecular organization of receptors and adenylate cyclase units in membranes. The model excludes a number of mechanistic proposals and suggests a new hypothesis for membrane coupling with features which may be generally applicable to other hormone-sensitive adenylate cyclase systems.

Adenylyl Cyclases↗
PubMed1977

Integrated control of hepatic glucose metabolism.

The rates of storage and release of carbohydrate by the liver are determined by the plasma concentrations of several blood-borne signals; most important are the concentrations of glucose, and of the hormones insulin and glucagon. To understand the complex control relationships of these three signals as they affect the liver, their individual dynamic influences have been determined experimentally, and the findings have been integrated by means of a computer simulation of the pathways of hepatic glycogen metabolism. The simulation studies have led to specific hypotheses about the biochemical effects of glucose and insulin on the liver. The simulation studies have also led to the conclusion that glucose exerts a rapid moment-to-moment influence on the rate of uptake of glucose by the liver. Insulin, however, by exerting a slower influence on the sensitivity of the liver to glucose, is very effective in "optimizing" the amount of glycogen which the liver stores during food intake. Thus, integrated experimental and simulation studies can lead to a view of a physiological regulating system which does not emerge from either approach used alone.-

Animals↗
PubMed1976

Simulation study of control of hepatic glycogen synthesis by glucose and insulin.

The plausibility of various hypotheses concerning the effects of glucow dynamic model of glucose metabolism in the liver. The model consisted of six compartments representing extracellular glucose, and intracellular glucose, glucose 6-phosphate, glucose 1-phosphate, uridine diphosphate glucose, obtained from literature reports, the model predicted values of intermediates which were close to those reported for the liver, sampled from fasting animals. The model predicts that glucose can generate significant glycogen deposition by engendering the inhibition of glucose-6-phosphatase, but not by mass action, glycogen synthase activation, or phosphorylase deactivation. The model predicts that, although insulin can inhibit glucose production by lowering phosphorylase and gluconeogenesis, only an insulin-mediated induction of glucokinase can account for insulin's action to potentiate the effect of glucose alone on glycogen synthesis.

Glucose↗
PubMedDate not supplied

Insulin secretion, obesity, and potential behavioral influences: results from the Insulin Resistance Atherosclerosis Study (IRAS).

BACKGROUND: This work was conducted to evaluate associations of insulin secretion with overall and central obesity, dietary fats, physical activity, and alcohol. METHODS: A frequently sampled intravenous glucose tolerance test (FSIGT) was used to assess acute insulin response to glucose (AIR) and insulin sensitivity (S(I)) among adult participants (n=675 with normal, NGT; n=332 with impaired glucose tolerance, IGT) in the Insulin Resistance Atherosclerosis Study (IRAS). Disposition index (DI) was calculated as the sum of the log-transformed AIR and S(I) to reflect pancreatic compensation for insulin resistance. Obesity was measured as body mass index (kg/m(2), BMI) and central fat distribution by waist circumference (cm). Dietary fat intake (total, saturated, polyunsaturated, oleic acid), physical activity, and alcohol intake were assessed by standardized interview. RESULTS: In unadjusted analyses, BMI and waist were each positively correlated with AIR among NGTs (r=0.26 and 0.23, respectively; p<0.0001) but correlations were weaker among the IGTs (r=0.10, NS; r=0.13, p<0.05 for BMI and waist, respectively). BMI and waist were inversely correlated with DI among NGTs (r=-0.13 and -0.20, respectively; p<0.0001) and among IGTs (r=-0.20 and -0.19, respectively, p<0.0001). Dietary fat variables were positively related, and alcohol was inversely related, to AIR among NGTs (p<0.01) but not among IGTs. With all factors considered simultaneously in a pooled analysis of IGTs and NGTs, waist, but not BMI, was positively associated with AIR (p<0.001) and inversely associated with DI (p<0.01). None of the behavioral variables were independently related to either outcome. CONCLUSION: Among non-diabetic patients, central obesity appears to be related to higher insulin secretion, but to lower capacity of the pancreas to respond to the ambient insulin resistance.

Adult↗
PubMedDate not supplied

PACBERG: an adaptive program for controlling the blood sugar.

PACBERG, a new computer program for automatically controlling (clamping) the blood sugar is described. The plasma glucose concentration is maintained at steady basal (euglycemic) or elevated (hyperglycemic) levels during various insulin infusions. To accomplish this, a minimal mathematical model of glucose kinetics is implemented on a minicomputer. From the measured time course of plasma glucose concentration, using the model, the program estimates the insulin-dependent increase in fractional disappearance rate of glucose (X). In addition the program calculates the rate of exogenous glucose infusion (INF) which must be infused in order to maintain the desired glucose concentration. The program successfully clamps glucose at desired basal or elevated levels. Furthermore, the variable X, provided as the PACBERG studies proceed, is a real-time measure of insulin action which can be used to calculate insulin sensitivity (SI). PACBERG was written in BASIC, but can also be implemented on programmable calculators.

Blood Glucose↗
PubMedDate not supplied

OPSEG: a general routine for smoothing and interpolating discrete biological data.

The optimal segments technique is a new approach to smoothing and interpolating between small numbers of discrete biological data. This method balances the degree of smoothness against the expected error of the observed data. The OPSEG computer program searches for the set of smoothed data points which will match the overall difference between the smoothed and observed data to an a priori estimate of the measurement error. The smoothed curve is described as a series of linked individual line segments. This approach is useful for the analysis of biological signals such as plasma measurements of hormone and metabolite concentration and has been applied to the development of assay standard curves.

Biometry↗