Search PubMed⌕ Search

Biomedical subjects

R N Bergman

Publications and source records attributed to R N Bergman.

At least 163 records · Page 9Linked to original sources
PubMed1986

The insulin sensitivity index in nondiabetic man. Correlation between clamp-derived and IVGTT-derived values.

Although the minimal-model-based insulin sensitivity index (S1) can be estimated from the results of a simple 180-min intravenous glucose tolerance test (IVGTT), its relationship to widely accepted but technically more difficult clamp-based techniques has not been resolved in humans. Therefore we measured S1 by standard IVGTT, modified IVGTT, and clamp methods in 10 nondiabetic men with %IBW of 109 +/- 12 (mean +/- SD). In the euglycemic clamp studies, insulin was infused to bring insulin levels (IRI) from basal, 8 +/- 4 microU/ml, to plateaus of 21 +/- 5 and 35 +/- 6 microU/ml. S1[clamp], measured as the increase in glucose (G) clearance per increase in IRI [delta INF/(delta IRI X G)], averaged 0.29 +/- 0.09 ml/kg X min per microU/ml. In the IVGTT studies, 300 mg/kg G was given as an i.v. bolus, and G and IRI were measured for 180 min; in the modified (mod) IVGTT, tolbutamide (300-500 mg) was given i.v. 20 min after the G to observe the effect of an IRI peak on G removal after G level was free of initial "mixing" effects. The S1 estimated by computer did not differ significantly between standard [(6.9 +/- 3.4) X 10(-4) min-1 per microU/ml] and modified [(6.7 +/- 3.5) X 10(-4) min-1 per microU/ml] tests, indicating no bias due to the differing insulin patterns and levels. There was a strong positive correlation between S1 (mod IVGTT) and S1(clamp): r = 0.84; N = 10; P less than 0.002. The correlation between S1(standard IVGTT) and S1(clamp) was 0.54, suggesting the modified test is less "noisy." Nonetheless, in eight euglycemic women with a wider range of adiposity, S1(standard IVGTT) has been significantly correlated with %IBW (r = -0.72) and basal IRI (r = -0.84). The correlation between S1 measures by clamp and IVGTT methods provides one step toward validation of the minimal model for studies of insulin action in man.

Adult↗
PubMed1985

Diminished in vitro responsiveness of circulating erythroid progenitor cells to insulin as an indicator of insulin resistance.

While insulin resistance is considered characteristic of extreme obesity, it may be more difficult to demonstrate in less severe forms of obesity. We studied five moderately obese individuals [mean body mass index (MBMI), 34.1 +/- 1.85 (+/- SE) kg/m2], one massively obese patient (BMI, 50.2 kg/m2), and seven age-matched normal subjects (MBMI, 22.4 +/- 0.93 kg/m2). While two of the obese patients had normal glucose tolerance, all had fasting hyperinsulinemia (P less than 0.02 vs. normal subjects) and exaggerated insulin responses after oral glucose challenge, as defined by area under the 3-h insulin response curve (P less than 0.01 vs. normal subjects). That this hyperinsulinemia represented in vivo insulin resistance was supported by the glucose and insulin responses in four individuals to an iv glucose bolus analyzed by the minimal modeling technique. Study of monocyte insulin receptors revealed no reduction in total insulin binding in the four obese patients tested. Since physiological concentrations of insulin stimulate the in vitro growth of normal human erythroid progenitor cells (EPC), we reasoned that this response might be blunted in cells from individuals with endogenous insulin resistance. The mean peak EPC proliferative response (26.7 +/- 9.11% above baseline) in the obese hyperinsulinemic group was significantly less than the corresponding mean value in the control group (92.6 +/- 5.24% above baseline, P less than 0.001). These results suggest that the minimal modeling technique is a sensitive method for the in vivo demonstration of insulin resistance in moderately obese individuals and that EPC responsiveness to physiological concentrations of insulin reflects in vivo insulin sensitivity and may be used as an in vitro indicator of insulin resistance.

Adolescent↗
PubMed1985

Pathogenesis of age-related glucose intolerance in man: insulin resistance and decreased beta-cell function.

To identify the pathogenic factors responsible for glucose intolerance of aging, we measured a variety of metabolic parameters, including insulin sensitivity and islet cell function, in 10 young (18-36 yr old) and 10 older (57-82 yr old) men of normal body weight. Subject groups had equivalent fasting plasma glucose and fat cell size values. Frequently sampled iv glucose tolerance tests were performed, and the data were analyzed by computer using the minimal model approach. This technique yields the following measures: SI, the insulin sensitivity index; phi 1 and phi 2, indices of first and second phase beta-cell responsiveness to glucose; n, fractional insulin clearance, and SG, a measure of dynamic glucose disappearance dependent on glucose per se. We also evaluated beta-cell responsiveness independently by measuring the plasma insulin response to arginine injections at three levels of glycemia and calculated potentiation slope from the relationship between the acute insulin response to arginine and the prestimulus glucose level. The older men were glucose intolerant (glucose disappearance rate, 1.32% min-1) compared to the younger men (glucose disappearance rate, 2.21% min-1; P less than 0.01). This intolerance was the result of both a beta-cell defect and insulin resistance. The potentiation slope (r = -0.67; P less than 0.02) and phi 2 (r = -0.47; P less than 0.05) both decreased with age. In addition, SI in the older group was diminished 63% (2.4 vs. 6.5; 10(-4) min-1/microU/ml; P less than 0.001) and was unrelated to differences in body fat. No differences were found in either n or SG. These studies suggest that the diminished glucose tolerance of aging in normal weight men has multifactorial causality. Both beta-cell dysfunction and insulin resistance are important. In contrast, we found little evidence for changes in insulin clearance or insulin-independent glucose disappearance contributing to age-related glucose intolerance.

Adipose Tissue↗
PubMed1985

Importance of glucose per se to intravenous glucose tolerance. Comparison of the minimal-model prediction with direct measurements.

Glucose disappearance after an oral or intravenous challenge is a function of the effects of both endogenously secreted insulin and of glucose itself. We previously introduced the term "glucose effectiveness," or SG, defined as the ability of glucose per se to enhance its own disappearance independent of an increment in plasma insulin. The present investigation, performed in conscious dogs, was undertaken to quantify this glucose effect by minimal-model-based analysis of insulin and glucose dynamics after a frequently sampled intravenous glucose tolerance test (FSIGT). The values from the standard FSIGT were then compared with direct measurements obtained from experiments in which the dynamic insulin response to glucose was suppressed with somatostatin (SRIF). In addition, we examined SG values from the modified FSIGT protocol, which involves both glucose and tolbutamide injections. Protocol l (N = 9): FSIGTs were performed and the glucose and insulin data were analyzed by computer. KG was 2.65 +/- 0.28 min-1, S1 was 4.09 +/- 0.34 X 10(4) min-1/(microU/ml), and SG was 0.033 +/- 0.004 min-1. Protocol II (N = 6): FSIGTs were performed on animals in which SRIF was infused (0.8 micrograms/min X kg) to obliterate the dynamic insulin response to glucose injection. Before the FSIGt, insulin and glucagon were infused intraportally to reattain basal glycemia. Without dynamic insulin, KG was reduced to 0.96 +/- 0.18 min-1 (P less than 0.0001). However, SG, estimated from the exponential rate of fall of plasma glucose in the absence of dynamic insulin, was similar to the standard FSIGTs: 0.025 +/- 0.004 (P greater than 0.25). Protocol III (N = 6): modified FSIGTs were performed using glucose and tolbutamide injections for a better estimate of model parameters. Model parameters Sl and SG, and the KG were not different from standard FSIGTs (P greater than 0.3). In fact, the value of SG (0.028 +/- 0.003 min-1) was nearly identical to the direct measure from protocol II. Therefore, the effect of glucose per se on glucose decline, estimated by modeling the standard and modified FSIGTs, was confirmed by a direct measurement with the endogenous insulin response suppressed with SRIF. Also, the time course of the insulin effect to enhance net glucose disappearance from plasma [Ieff(t)] was calculated from the data of protocol II, and was the same as the time course predicted by the model. These studies demonstrate the ability of the computer modeling approach to separate insulin-dependent and glucose-dependent glucose disappearance, and represent a direct confirmation of the minimal model.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Extrapancreatic effect of somatostatin infusion to increase glucose clearance.

Constant intraportal insulin, coupled with variable intraportal glucagon, was used in the attempt to reestablish basal metabolic conditions in dogs during somatostatin (SRIF) infusion (0.8 micrograms X min-1 X kg-1). SRIF alone lowered glucose (G), insulin (I), and glucagon (GN) (G: 90 +/- 5 to 69 +/- 1 mg/dl; I: 18 +/- 4 to 4 +/- 1 microU/ml; GN: 257 +/- 52 to 168 +/- 40 pg/ml; P less than 0.05 or better). Hormone replacement. Hypoglycemia persisted (G at steady state, SS, 60-150 min): 12 +/- 3 mg/dl below basal; P = 0.006) despite intraportal insulin replacement (200 microU X min-1 X kg-1; insulin at basal: 14 +/- 1; at SS: 14 +/- 2 microU/ml; P greater than 0.9) and glucagon overreplacement (basal: 341 +/- 42; SS: 486 +/- 80 pg/ml; P less than 0.05). Glucose clearance was increased 65% above basal (P less than 0.0001). Insulin underreplacement. With a lower intraportal insulin infusion rate (50 microU X min-1 X kg-1), insulin fell from basal (10 +/- 2 microU/ml) to 4 +/- 1 microU/ml during steady state (P = 0.03). Glucose and glucose clearance were normalized to basal values (G: 85 +/- 3 mg/dl, P = 0.3; clearance: 5.7 +/- 0.5 ml X min-1 X kg-1; P = 0.2) with full glucagon replacement (basal: 281 +/- 120; SS: 264 +/- 80 pg/ml; P greater than 0.9). Thus, during constant SRIF infusion, normoglycemia was reattained when insulin was underreplaced via the portal vein. The failure to reattain euglycemia with normoinsulinemia was due to a SRIF-induced increase in extrahepatic glucose clearance. Insulin replacement and growth hormone (GH) infusion. GH (15 ng X min-1 X kg-1) partially reversed the hypoglycemia during SRIF, with full insulin replacement. The SRIF-induced increase in glucose clearance may be partially mediated by a decrease in GH.

Animals↗
PubMed1984

The insulin sensitivity index. Correlation in dogs between values determined from the intravenous glucose tolerance test and the euglycemic glucose clamp.

We previously proposed the insulin sensitivity index, Sl, as an absolute measure of whole body tissue sensitivity to insulin. Sl is defined, in the physiologic range of insulin action, as the effect of insulin to augment glucose's ability to reduce its own plasma level. This parameter can be determined from the frequently sampled intravenous glucose tolerance test (IVGTT) by using a digital computer to find the coefficients of a minimal mathematical model of glucose kinetics. In the present study we compared, in normal dogs, Sl determined from the IVGTT to an analogous parameter [Sl(clamp)] calculated from the euglycemic glucose clamp (EGC). Fifteen pairs of experiments (1 IVGTT and 1 EGC) were performed on 12 animals. IVGTTs: After glucose injection (0.3 g/kg), frequent blood samples were taken over the subsequent 3 h. KG ranged from 1.7 to 4.7%/min, and integrated insulin from 0.4 to 5.9 (mU/ml) min for 0-60 min. Sl varied over a nine-fold range from 1.0 to 9.1 X 10(-4) (min-1)/(microU/ml), with a mean of 4.3 +/- 0.7 X 10(-4). Fractional glucose disappearance rate independent of insulin (p1) was 4.3 +/- 0.5%/min. EGCs: Low-rate insulin infusion (8 mU/min from 1 to 150 min) elevated plasma insulin (INS) from 15 +/- 4 to 43 +/- 10 microU/ml. Glucose was infused (GINF) at 119 +/- 20 mg/min to maintain euglycemia. Moderate insulin infusion (40 mU/min: 151-300 min) further elevated plasma insulin (to 176 +/- 37 microU/ml) and the requisite glucose infusion (to 372 +/- 36 mg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Optimal segments: a method for smoothing tracer data to calculate metabolic fluxes.

Metabolic fluxes (Ra and Rd) are calculated in the nonsteady state using Steele's equations. These calculations require estimates of the values and rates of change of glucose and specific activity at discrete sampling times. Data smoothing minimizes the effect of measurement error that confounds the Ra and Rd calculations. We compared three smoothing methods: a) moving average, b) polynomial fitting, and c) optimal segments, a new technique that utilizes optimization methods. Experimental designs were simulated: 1) constant infusion of glucagon in depancreatized dogs, and 2) glucose oscillations generated by constant high-level glucose infusion. Measurement error was added to raw data. After smoothing, fluxes were calculated and compared to the "actual" Ra and Rd. Ra calculated from unsmoothed noisy data were in error by an average 39%. Error was reduced by smoothing to: 23%, moving average; 18%, polynomial fitting; 15%, optimal segments. Optimal segments was best for calculating Ra (P less than 0.01) and was better than or equal to other methods for Rd. Distortion in flux patterns was greatest for polynomial fitting (P less than 0.01) and least for optimal segments (P less than 0.001). Optimal segments is the method of choice for smoothing tracer data; it improves calculations of Ra and Rd with minimal distortion.

Animals↗
PubMed1982

Intraportal glucose infusion matched to oral glucose absorption. Lack of evidence for "gut factor" involvement in hepatic glucose storage.

These studies were designed to test whether a putative gastrointestinal factor (separate from that stimulating insulin release) is involved in the enhancement of liver glycogen storage during oral glucose ingestion. To do this, we compared net hepatic glucose uptake in conscious dogs, following oral glucose administration, with hepatic uptake during intraportal glucose infusion. The rate of intraportal glucose infusion was calculated to match the time course of gut glucose absorption in the oral administration experiments. In control studies, intragastric instillation of tap water [90 +/- 2.4 (SE) in four dogs had no effect on basal rates of gastrointestinal (GI) glucose uptake (16 +/- 1 mg/min) oe hepatic glucose production (97 +/- 3 mq/min). Net basal GI lactate production was equal to GI glucose utilization (P greater than 0.1); glycolytic conversion of glucose to lactate accounted for all basal GI glucose utilization. In oral experiments, gastric instillation of 1.2 g/kg glucose (N = 8) caused GI glucose absorption to increase within 5 min (P less than 0.01). Net glucose absorption from the gut was maximal (355 1.55 mg/min) at 60 min, and was complete at 165-240 min (mean = 186 min). During absorption, liver switched from production to net uptake by 30 min (P less than 0.01); production was resumed by 3 h. Total glucose taken up by liver was 7.19 +/- 1.8 g (23% oral load). No net metabolism of the instilled glucose to lactate occurred during absorption; GI lactate production was the same during absorption (13.0 +/- 5.0 mg/min) as before glucose instillation (11.2 +/- 2.0 mg/min; P greater than 0.45). In intraportal experiments, intraportal glucose infusion (total = 1.09 g/kg) induced liver to take up glucose by 15 min (P less than 0.01); total hepatic uptake (4.6 +/- 1.5 g) was not significantly different from the oral experiments (P greater than 0.15). Also, nonsplanchnic glucose uptake was the same in the oral (25.1 +/- 2.2) and intraportal (25.2 +/- 1.4) studies. The lack of difference between hepatic and extrahepatic fates of administered glucose with oral and intraportal administration indicates that no putative gut factor need be invoked to explain hepatic glycogen deposition during oral glucose, and it seems probable that no such factor exists in the dog.

Administration, Oral↗
PubMed1982

A minimal-model-based glucose clamp yielding insulin sensitivity independent of glycemia.

A new technique is introduced for automatic control of the blood sugar ("glucose clamp") at basal (euglycemic) or elevated (hyperglycemic) levels during variable insulin infusion. A minimal mathematical model of glucose kinetics is implemented on a laboratory minicomputer during clamp experiments. From the measured time course of plasma glucose concentration, the computer estimates the fractional disappearance rate of glucose (X) and calculates the rate of exogenous infusion required to match the desired concentration (M). Eight clamp experiments were performed on three conscious dogs. Euglycemic (N = 4): insulin was infused at 8, 40, and 150 microU/min for sequential 2.5-h periods )I, II, and III); hyperglycemic (N = 4): following the establishment of 140 mg/dl hyperglycemia (period I), insulin was infused at 30 and 120 mU/min for 2.5 h each (periods II and III). Plasma insulin levels [range: 21 +/- 9 (basal) to 1729 +/- 209 microunits/ml] were matched in comparable periods in the two types of experiments [P greater than 0.8 (I); P greater than 0.5 (II), P greater than 0.2 (III)]. Glucose was successfully clamped for all periods at euglycemia (99.6 +/- 0.7% of desired value) and hyperglycemia (100.0 +/- 1.1% desired 140-mg/dl value). Glucose infusion rates necessary to achieve stable glycemia were greater at elevated than basal glucose (P less than 0.001) despite comparable insulinemia during the three insulin infusion periods. Thus, the glucose infusion rate versus insulin level (M/I) was glycemia-dependent, and therefore not a direct measure of insulin sensitivity. In contrast, the insulin-induced increases in fractional glucose disappearance (delta X), also provided by our clamp technique during experiments, were highly correlated within insulin (r = 0.08 to r = 0.99, P less than 0.01) and independent of glycemia (P greater than 0.7). The ratio delta X/delta I (increase in glucose fractional disappearance rate/incremental insulin level) was a measure of insulin sensitivity independent of glycemia, and could successfully differentiate insulin-resistant from normal animals (P less than 0.001; delta X/delta I in three animals: 6.9 X 10(-4), 5.5 X 10(-4), and 1.4 X 10(-4) min-1 microunits/ml). Thus, this model-dependent glucose clamp technique provides a direct measurement of insulin sensitivity independent of glycemia.

Animals↗
PubMed1981

Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose.

The quantitative contributions of pancreatic responsiveness and insulin sensitivity to glucose tolerance were measured using the "minimal modeling technique" in 18 lean and obese subjects (88-206% ideal body wt). The individual contributions of insulin secretion and action were measured by interpreting the dynamics of plasma glucose and insulin during the intravenous glucose tolerance test in terms of two mathematical models. One, the insulin kinetics model, yields parameters of first-phase (phi 1) and second-phase (phi 2) responsivity of the beta-cells to glucose. The other glucose kinetics model yields the insulin sensitivity parameters, SI. Lean and obese subjects were subdivided into good (KG greater than 1.5) and lower (KG less than 1.5) glucose tolerance groups. The etiology of lower glucose tolerance was entirely different in lean and obese subjects. Lean, lower tolerance was related to pancreatic insufficiency (phi 2 77% lower than in good tolerance controls [P less than 0.03]), but insulin sensitivity was normal (P greater than 0.5). In contrast, obese lower tolerance was entirely due to insulin resistance (SI diminished 60% [P less than 0.01]); pancreatic responsiveness was not different from lean, good tolerance controls (phi 1: P greater than 0.06; phi 2: P greater than 0.40). Subjects (regardless of weight) could be segregated into good and lower tolerance by the product of second-phase beta-cell responsivity and insulin sensitivity (phi 2 . SI). Thus, these two factors were primarily responsible for overall determination of glucose tolerance. The effect of phi 1 was to modulate the KG value within those groups whose overall tolerance was determined by phi 2 . SI. This phi 1 modulating influence was more pronounced among insulin sensitive (phi 1 vs. KG, r = 0.79) than insulin resistant (obese, low tolerance; phi 1 vs. KG, r = 0.91) subjects. This study demonstrates the feasibility of the minimal model technique to determine the etiology of impaired glucose tolerance.

Body Weight↗
PubMed1980

Cause of glucose oscillations during glucose infusion: periodic variation in glucose uptake.

Constant infusion of glucose (10 mg . kg-1 . min-1) into conscious, intact dogs induced oscillations in the plasma concentrations of glucose and insulin. Glucose rose from basal (98 +/- 1 mg/dl) and, after 3 h, entered oscillations that persisted until the end of the 9-h glucose infusion. Between 240 and 540 min, glucose fluctuated by +/- 17 mg/dl about a mean value of 143 +/- 2 mg/dl; frequency of the glucose oscillation was 0.54 +/- 0.03 cycles/h. During the same time interval, insulin increased from basal 13 +/- 2 mu U/ml to mean 46 +/- 4 mu U/ml. Insulin oscillated at an amplitude (peak-to-peak) of 48 mu U/ml, with frequency not different from that of glucose (0.60 +/- 0.09 cycles/h). The oscillation in glucose "led" the insulin oscillation by 22 +/- 5 min. In three animals, [2-3H]glucose was infused along with unlabeled glucose during oscillations, and it was determined that almost all (98%) of the glucose appearance was from the exogenous infusion. Thus varying endogenous glucose production was ruled out as a contributory factor to the glucose oscillation. Total glucose uptake (Rd) fluctuated periodically at the same frequency as glucose and insulin (0.56 +/- 0.05 cycles/h) and with a large amplitude (Rd mean = 248 mg/min; peak-to-peak amplitude = 85 mg/min). Direct splanchnic balance measurements were made in the interval 240-540 min to determine the specific contributions of splanchnic (Rds) and peripheral glucose uptake (Rdp) to the oscillation in total Rd. Peripheral uptake oscillated in phase with plasma insulin and accounted for 80% (57.5 g) of total Rd. The splanchnic bed (presumably liver) sequestered 20% (14.1 g) of infused glucose, and Rds varied in phase with plasma glucose. The liver extracted 5.6 +/- 0.3% of the total amount of glucose presented to it in the 5-h interval of observation. It is concluded that a) large fluctuations in peripheral glucose utilization are responsible for the observed periodicities in glucose concentration; b) peripheral uptake fluctuations result from periodic bursts in insulin secretion; c) during glucose infusion, glucose is the primary moment-to-moment regulator of hepatic glucose uptake, whereas insulin is the principal regulator of peripheral glucose utilization.

Animals↗
PubMed1980

Quantitative estimation of beta cell sensitivity to glucose in the intact organism: a minimal model of insulin kinetics in the dog.

We propose an approach to quantifying the sensitivity of B cells to glucose in the intact organism, whereby we interpret the complex dynamic plasma insulin response to glucose injection in terms of a minimal mathematical model of posthepatic insulin delivery and insulin clearance. The best model for this purpose was chosen by comparing the ability of a series of proposed models to account precisely for plasma insulin dynamics. Intravenous glucose tolerance tests (IVGTT) (300 mg/kg) were performed on conscious dogs, and blood was sampled frequently until the basal steady state was reestablished. Glucose injection produced variable plasma insulin responses, which were characterized by an early peak (76 microU/ml above basal), a plateau with occasional additional peaks, and by an abrupt return of plasma insulin to basal by 37 min. A set of eight models was examined; one emerged as superior, in that it was able to account for insulin dynamics with the smallest number of physiologically meaningful parameters (N = 4). The chosen (minimal) model assumes that (1) clearance of insulin is of the first order, (2) the initial peak represents a bolus of insulin loaded into the plasma after the glucose injection, and (3) the rate of the secondary rise in insulin is determined by the concentration of glucose in plasma above a specific threshold value. The sensitivity of first phase insulin delivery to glucose (phi 1; 1.28 +/- 0.15 microU/ml per min per mg/dl), the sensitivity of the secondary phase to glucose concentration [phi 2; 0.038 +/- 0.005 (microU/mg) . min-2], and the threshold for glucose stimulation of second phase secretion (h; 125 +/- 8 mg/100 ml) were all precisely estimated from the dynamic insulin responses. These three parameters of insulin kinetics (phi 1, phi 2, and h) can be calculated from a single IVGTT, and they characterize the insulin responsiveness of a single individual. Estimating these characteristic parameters of insulin kinetics from IVGTT data has potential for quantitating the individual factors contributing to glucose-stimulated insulin secretion in intact animal models, and it may be applicable to man.

Animals↗
PubMed1980

Effect of insulin, glucose, and 2-deoxy-glucose infusion into the third cerebral ventricle of conscious dogs on plasma insulin, glucose, and free fatty acids.

Previous studies have demonstrated that exogenous insulin, injected into central cerebrospinal fluid cavities of dogs, stimulates the release of endogenous insulin from the pancreas. To determine whether this response was elicited by (1) insulin per se, (2) an effect of insulin on glucose transport, or (3) glucopenia in the cerebrospinal fluid, we measured plasma insulin, glucose, and free fatty acids during the infusion of insulin, glucose, and 2-deoxy-glucose (2DG), individually or in combination, into the third cerebral ventricle of conscious dogs. As expected, the third ventricular infusion of insulin alone elicited a small, but significant, rise of plasma insulin. Surprisingly, infusion of insulin with glucose produced a smaller increase of plasma insulin (P less than 0.05) and the infusion of insulin with 2DG produced a much larger increase of plasma insulin (P less than 0.05) than did the third ventricular infusion of insulin alone. The third ventricular infusion of either glucose alone or 2DG alone had no effect on the plasma levels of insulin. These data suggest that administration of insulin into the cerebral ventricles stimulates pancreatic insulin secretion but not by accelerating the transport of glucose into a chemosensitive area of the brain.

Animals↗
PubMed1979

Caval occlusion technique for hepatic venous sampling: a new approach to estimating splanchnic substrate balance in conscious dogs.

We have proposed a new technique for sampling hepatic venous blood in conscious dogs. Sub-hepatic vena caval blood flow was temporarily occluded by a previously implanted inflatable snare so that all blood entering the inferior vena cava was hepatic venous effluent. Hepatic venous blood samples were collected from the inferior vena cava 8 seconds after beginning caval occlusion, with the total interval of flow occlusion lasting 12 to 15 seconds. No behavioral or metabolic alterations were observed when or metabolic alterations were observed when hepatic venous effluent was repetitively sampled using the caval occlusion technique. Net splanchnic glucose balance (NSGB) was measured in conscious dogs receiving saline, glucose or glucagon infusions. NSGB measurements made with the caval occlusion technique were in accord with previous results obtained via tracer methodology or arterio-venous difference techniques utilizing hepatic vein catheterization. The caval occlusion technique thus provides a method for collecting hepatic venous blood samples from conscious animals without the difficulties associated with hepatic vein catheterization.

Abdomen↗