PubMed Health⌕ Search

Biomedical subjects

M W Schwartz

Publications and source records attributed to M W Schwartz.

At least 19 recordsLinked to original sources
PubMed1992

Short-term hyperglycemia and hyperinsulinemia improve insulin action but do not alter glucose action in normal humans.

Tissue glucose uptake occurs by insulin-dependent and insulin-independent mechanisms. To evaluate the effect of mild hyperglycemia and hyperinsulinemia on the parameters responsible for glucose disposal, glucose (1.17 mmol/min) or saline was infused into six healthy male subjects (age 25-38 yr, body mass index 22.1-26.3 kg/m2) for 24 h. Thereafter, while the infusion continued, indexes of insulin sensitivity (SI), glucose effectiveness at basal insulin (SG), basal insulin effect (BIE = SI x basal insulin), and glucose effectiveness at zero insulin (GEZI = SG - BIE) were measured using Bergman's minimal model of insulin action. GEZI provides a measure of the efficiency of glucose to accelerate its own disposal independent of insulin. Twenty-four hours of glucose infusion increased the basal plasma glucose (5.1 +/- 0.1 to 6.4 +/- 0.2 mM, P = 0.001) and insulin (79 +/- 8 to 174 +/- 31 pM, P less than 0.05) levels. Hyperglycemia was also associated with an increase in the insulin response, predominantly in the second-phase component (138 +/- 31 to 258 +/- 66 pM, P less than 0.05). SI (4.8 +/- 1.0 to 8.2 +/- 1.6 x 10(-5) min-1.pM-1, P less than 0.05) and SG (1.7 +/- 0.1 to 2.5 +/- 0.3 x 10(-2) min-1, P less than 0.05) both increased after glucose infusion. The increase in SG was entirely due to the combined increase in basal insulin and insulin sensitivity (BIE 0.4 +/- 0.1 to 1.2 +/- 0.1 x 10(-2) min-1, P = 0.001) since GEZI did not change at all (1.3 +/- 0.1 vs. 1.3 +/- 0.3 x 10(-2) min-1, P = not significant). From these data we conclude that, in normal subjects, the mild hyperglycemia and hyperinsulinemia occurring during a prolonged glucose infusion improves glucose disposal in the basal state by increasing insulin secretion and insulin sensitivity but does not enhance glucose effectiveness independent of insulin. Both of these changes thus tend to minimize the development of hyperglycemia.

Adult↗
PubMed1992

Inhibition of hypothalamic neuropeptide Y gene expression by insulin.

Insulin acts in the brain to suppress feeding, whereas neuropeptide Y (NPY) has the opposite effect. Since fasting lowers plasma insulin levels and increases hypothalamic synthesis of NPY, we proposed that insulin may inhibit hypothalamic NPY gene expression. To test this hypothesis, we used RIA and in situ hybridization histochemistry to determine if centrally administered insulin could reduce levels of both NPY and its messenger RNA (mRNA) in discreet hypothalamic regions during fasting. Three groups of Long-Evans rats were entered into a 72-h study protocol. One group was fed ad libitum during this period, while the others were fasted. Fed rats received intracerebroventricular (icv) injections of saline vehicle at 12-h intervals, whereas fasted groups received icv vehicle alone or with insulin (4 mU/12 h). In vehicle-only treated rats, fasting significantly increased expression of preproNPY mRNA in the arcuate nucleus to 179 +/- 20% of fed controls. Administration of icv insulin during fasting abolished this increase (99 +/- 14% of fed controls; P less than 0.05 vs. fasted, vehicle-treated rats). Central insulin administration during fasting also reduced immunoreactive NPY concentrations in samples punched from the paraventricular nucleus (PVN) (875 +/- 122 pg/punch) to levels below vehicle-only treated rats (1396 +/- 435 pg/punch; P less than 0.05), similar to free-feeding control values (814 +/- 170 pg/punch). By comparison, neither fasting nor central insulin administration altered NPY levels in four other hypothalamic regions (supraoptic, ventromedial, dorsomedial, and arcuate nuclei). Continuous icv insulin infusion at a lower dose (2 mU/day) produced a similar result during a shorter period (48 h) of food deprivation in Wistar rats. In this study, central insulin infusion also inhibited the fasting-related increase in arcuate preproNPY mRNA levels and did not affect plasma glucose or insulin levels. This suggests that insulin acts locally to inhibit hypothalamic NPY mRNA expression. We conclude that the increase of levels of NPY in the PVN and preproNPY mRNA in the arcuate nucleus during fasting are inhibited by icv insulin. Fasting, therefore, increases NPY biosynthesis along an arcuate nucleus-PVN pathway in the hypothalamus via a mechanism dependent on low insulin levels.

Animals↗
PubMed1992

Effect of insulin resistance and hyperglycemia on proinsulin release in a primate model of diabetes mellitus.

An elevated plasma proinsulin (PI) to immunoreactive insulin (IRI) ratio occurs in relatives of patients with insulin-dependent diabetes mellitus and in subjects with non-insulin-dependent diabetes mellitus. To determine whether this alteration is the result of B-cell dysfunction and/or insulin resistance, we infused nicotinic acid for 3 weeks to produce insulin resistance in five adolescent male baboons before and after the administration of streptozocin (200 mg/kg). We measured basal PI and IRI levels and the acute incremental PI (APIR) and IRI (AIRIR) responses to iv arginine. The quantity of IRI comprised of PI was calculated in the basal state (PI/IRI) and following arginine injection (APIR/AIRIR). Streptozocin administration did not change the fasting plasma glucose (FPG) compared to that in the normal animals (4.7 +/- 0.3 vs. 4.3 +/- 0.2 mM) but raised the PI/IRI (16.4 +/- 3.4 vs. 5.9 +/- 1.7%) and APIR/AIRIR (7.1 +/- 1.0 vs. 2.8 +/- 1.0%) due to a concurrent reduction in IRI and increase in PI concentrations. The induction of experimental insulin resistance with nicotinic acid in the normal animals had no effect on the FPG (4.4 +/- 0.2 mM) but in the streptozocin treated animals, fasting hyperglycemia (8.3 +/- 1.7 mM) developed. Neither the basal PI/IRI (10.2 +/- 2.2%) or the APIR/AIRIR (2.3 +/- 0.6%) increased in the insulin-resistant streptozocin animals thus being no different to that of normal control animals before or during experimental insulin resistance. We conclude that disproportionate proinsulinemia is a manifestation of B-cell damage from streptozocin which is not exacerbated by insulin resistance or hyperglycemia.

Animals↗
PubMed1991

Effect of nicotinic acid-induced insulin resistance on pancreatic B cell function in normal and streptozocin-treated baboons.

To study the interaction between insulin secretion and insulin action in maintaining glucose homeostasis, we induced experimental insulin resistance in eight normal baboons, in six baboons treated with 40 mg/kg streptozocin (STZ-40), and in six baboons treated with 200 mg/kg streptozocin (STZ-200). Insulin resistance was induced by a 20-d continuous intravenous infusion of nicotinic acid (NA). Normal animals showed compensatory increases in several measures of insulin secretion (fasting insulin [FI], acute insulin response to arginine [AIRarg], acute insulin response to glucose [AIRgluc], and glucose potentiation slope [delta AIRarg/delta G]), with no net change in fasting plasma glucose (FPG) or glycosylated hemoglobin (HbAtc). STZ-40 animals showed compensatory increases in FI, AIRarg, and AIRgluc, but delta AIRarg/delta G failed to compensate. Although FPG remained normal in this group during NA infusion, HbA1c rose significantly. STZ-200 animals failed to show compensatory changes in both AIRgluc and delta AIRarg/delta G, with both HbA1c and FPG rising. These animals showed a paradoxical inhibition of insulin secretion in response to intravenous glucose during NA infusion, at a time when they were hyperglycemic. These data indicate that a significant degree of insulin resistance does not cause hyperglycemia in the presence of normal B cell function but, in animals with reduced B cell mass and superimposed insulin resistance, the degree of hyperglycemia is proportional to the degree of pancreatic B cell dysfunction.

Animals↗
PubMed1991

Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport.

To study the route by which plasma insulin enters cerebrospinal fluid (CSF), the kinetics of uptake from plasma into cisternal CSF of both insulin and [14C]inulin were analyzed during intravenous infusion in anesthetized dogs. Four different mathematical models were used: three based on a two-compartment system (transport directly across the blood-CSF barrier by nonsaturable, saturable, or a combination of both mechanisms) and a fourth based on three compartments (uptake via an intermediate compartment). The kinetics of CSF uptake of [14C]inulin infused according to an "impulse" protocol were accurately accounted for only by the nonsaturable two-compartment model (determination coefficient [R2] = 0.879 +/- 0.044; mean +/- SEM; n = 5), consistent with uptake via diffusion across the blood-CSF barrier. When the same infusion protocol and model were used to analyze the kinetics of insulin uptake, the data fit (R2 = 0.671 +/- 0.037; n = 10) was significantly worse than that obtained with [14C]inulin (P = 0.02). Addition of a saturable component of uptake to the two-compartment model improved this fit, but was clearly inadequate for a subset of insulin infusion studies. In contrast, the three-compartment model accurately accounted for CSF insulin uptake in each study, regardless of infusion protocol (impulse infusion R2 = 0.947 +/- 0.026; n = 10; P less than 0.0001 vs. each two-compartment model; sustained infusion R2 = 0.981 +/- 0.003; n = 5). Thus, a model in which insulin passes through an intermediate compartment en route from plasma to CSF, as a part of a specialized transport system for the delivery of insulin to the brain, best accounts for the dynamics of this uptake process. This intermediate compartment could reside within the blood-CSF barrier or it may represent brain interstitial fluid, if CNS insulin uptake occurs preferentially across the blood-brain barrier.

Animals↗
PubMed1991

Central insulin administration reduces neuropeptide Y mRNA expression in the arcuate nucleus of food-deprived lean (Fa/Fa) but not obese (fa/fa) Zucker rats.

By acting in the brain, insulin suppresses food intake, whereas neuropeptide Y (NPY) has the opposite effect. Since fasting increases NPY gene expression in the hypothalamic arcuate nucleus (ARC) and also lowers circulating insulin levels, we hypothesized that the anorexiant effect of insulin could result from insulin inhibition of NPY gene transcription in the ARC. Therefore, we determined whether the administration of insulin (200 mU per 12 hrs) into the 3rd cerebral ventricle of lean (Fa/Fa) female Zucker rats (n = 5) during 48 hrs of food deprivation reduces the expression of preproNPY mRNA in the ARC compared to vehicle-treated controls (n = 5). Coronal sections of rat brain were hybridized with an oligonucleotide probe complementary to preproNPY mRNA and apposed to x-ray film. Hybridization was quantified in both the ARC and the hippocampal dentate gyrus by computerized image analysis of the resulting autoradiographs. Central insulin significantly reduced the area of hybridization in the ARC (0.235 +/- 0.017 mm2; mean +/- SE) compared to vehicle-treated controls (0.331 +/- 0.037 mm2; p less than 0.05), but was without effect in the hippocampus. Thus, insulin reduced the expression of mRNA for NPY specifically in the ARC. Since the genetically obese (fa/fa) Zucker rat is insensitive to the anorexiant effect of insulin and over-expresses NPY in the ARC, we next tested the hypothesis that insulin does not suppress NPY mRNA expression in the ARC of these rats. Consistent with this hypothesis, central insulin administration to obese Zucker rats during 48 hrs of food deprivation (n = 6) did not lower hybridization area in the ARC compared to vehicle alone (n = 4) (0.286 +/- 0.036 vs. 0.248 +/- 0.019 mm2; p greater than 0.05). We conclude that insulin suppresses the expression of mRNA for NPY in the ARC of fasted lean but not obese Zucker rats. Regulation of hypothalamic NPY gene expression by insulin may account for its anorexiant effect, and a defect in this action may contribute to certain forms of obesity.

Animals↗
PubMed1990

Kinetics and specificity of insulin uptake from plasma into cerebrospinal fluid.

To characterize the relationship between insulin levels in plasma and those in cerebrospinal fluid (CSF), we studied the kinetics of both the uptake of insulin into CSF from plasma and the turnover of insulin within the CSF compartment. Sustained physiological levels of euglycemic hyperinsulinemia (plasma insulin approximately 500 pM) did not alter CSF insulin levels within the 1st h, but by 90 min a significant increase was observed (P less than 0.01). During graded hyperinsulinemic clamps (mean plasma insulin approximately 500-15,000 pM), CSF insulin rose in a dose-dependent fashion. This rise was characterized by an initial delay followed by a continuous increase for the next 150 min. We also found that after brief, high-dose intravenous insulin infusions, the t1/2 of CSF insulin was 143 +/- 7 min (means +/- SE; n = 4), similar to that of CSF turnover by bulk flow. To test the specificity of CSF insulin uptake from plasma, we compared this uptake during intravenous insulin infusions with that of proinsulin, a peptide with reduced affinity for the insulin receptor. We observed a significantly lower increment of CSF proinsulin levels over 180 min (13.6 +/- 1.6 pM; means +/- SE; n = 4) compared with that of insulin (22.4 +/- 0.6 pM; n = 4; P less than 0.01), despite plasma proinsulin levels higher than insulin (1,890 +/- 287 vs. 1,283 +/- 192 pM; P less than 0.001). When corrected for the difference in plasma levels, the uptake of insulin was fivefold greater than that of proinsulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus.

Fasting serum total immunoreactive insulin (IRI), true insulin, and true proinsulin (PI) were measured in 169 Pima Indians. The relationship of these variables to glucose tolerance, obesity, and parental diabetes was studied. Seventy-seven subjects had normal glucose tolerance, 46 had impaired glucose tolerance (IGT), and 46 had noninsulin-dependent diabetes mellitus (NIDDM) by WHO criteria. In subjects with normal glucose tolerance, the geometric mean ratio of PI to IRI (PI/IRI) was 10.8% (arithmetic mean, 12.5%), similar to that reported in other ethnic groups with lower prevalence rates of NIDDM. Parental diabetes had no effect on PI/IRI. Obese persons (body mass index, greater than or equal to 27 kg/m2) with normal glucose tolerance had PI/IRI of 9.3% compared with 16.3% for the nonobese (P less than 0.001), and PI/IRI was negatively correlated with body mass index (r = -0.34; P = 0.002). Proinsulin was disproportionately elevated in NIDDM (geometric mean PI/IRI, 19.9%; arithmetic mean, 23.6%), and the degree of elevation was related to the severity of hyperglycemia, but not the duration of diabetes. Subjects with IGT were more obese and had higher fasting plasma glucose (5.7 vs. 5.2 mmol/L; P = 0.025), true insulin (250 vs. 125 pmol/L; P less than 0.001), and PI concentrations (26 vs. 15 pmol/L; P less than 0.001) than those with normal glucose tolerance but similar mean PI/IRI (9.4 vs. 10.8%; P = 0.4). These findings indicate that Pima Indians with NIDDM have a disproportionate elevation of PI consistent with the hypothesis that beta-cell dysfunction associated with hyperglycemia leads to the release of proinsulin-rich immature granules.

Adolescent↗
PubMed1990

Treatment with a somatostatin analog decreases pancreatic B-cell and whole body sensitivity to glucose.

To determine the specific alteration in B-cell function caused by a somatostatin analog in man and to determine the effect of the induced insulin deficiency on insulin action, we administered octreotide (SMS 201-995; 50 micrograms twice daily) to nine healthy male subjects, aged 24-35 yr. B-Cell function was assessed by measuring the acute insulin response (AIR) to glucose (AIRglucose) at fasting glucose and to arginine (AIRarg) at glucose concentrations of fasting, approximately 14 and more than 28 mM after 2 (n = 7) and 8 days (n = 9) of octreotide. The AIRarg at more than 28 mM glucose (AIR500) is an estimate of B-cell secretory capacity, while the glucose level at which 50% of AIR500 occurs is termed PG50 and can provide an estimate of B-cell glucose sensitivity. Insulin sensitivity and the parameters describing glucose disposal were measured using Bergman's minimal model. Octreotide administration resulted in the development of mild fasting hyperglycemia, marked fasting hypoinsulinemia, as well as a marked reduction in AIRglucose [mean +/- SE; pretreatment, 260 +/- 48 pM; 1 day, 62 +/- 14 pM (P less than 0.005 vs. pretreatment); 8 days, 62 +/- 7 pM (P less than 0.005 vs. pretreatment)]. In addition, there was an associated marked reduction in iv glucose tolerance. While the AIRarg at fasting glucose (pretreatment, 233 +/- 27 pM; 2 days, 144 +/- 27 pM; 8 days 281 +/- 55 pM) and AIR500 (pretreatment 1000 +/- 178 pM; 2 days, 651 +/- 82 pM; 8 days, 1041 +/- 219 pM) remained unchanged, the AIRarg at 14 mM decreased significantly during octreotide [pretreatment 986 +/- 178 pM; 2 days, 363 +/- 62 pM (P less than 0.001 vs. pretreatment); 8 days, 623 +/- 130 pM (P less than 0.005 vs. pretreatment)], resulting in a rightward shift of the dose-response curve such that the estimated PG50 increased from 8.8 +/- 0.6 to 12.9 +/- 1.3 mM (P less than 0.05) after 2 days and was maintained for 8 days (11.2 +/- 0.8 mM; P less than 0.05 vs. pretreatment). Despite the development of marked insulin deficiency, the insulin sensitivity index (SI) did not change significantly (pretreatment, 11.34 +/- 1.59 x 10(-5); 1 day, 10.01 +/- 2.28 x 10(-5); 7 days, 9.65 +/- 1.69 x 10(-5) min-1/pM).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells.

Islet amyloid polypeptide (IAPP) has been identified as the major constituent of the pancreatic amyloid of non-insulin-dependent diabetes mellitus (NIDDM) and is also present in normal beta-cell secretory granules. To determine whether IAPP is a pancreatic secretory product, we measured the quantity of IAPP-like immunoreactivity (IAPP-LI), insulin, and glucagon released into 5 ml of incubation medium during a 2-h incubation of monolayer cultures (n = 5) of neonatal (3- to 5-day-old) Sprague-Dawley rat pancreases under three conditions: 1.67 mM glucose, 16.7 mM glucose, and 16.7 mM glucose plus 10 mM arginine and 0.1 mM isobutylmethylxanthine (IBMX). The quantity of IAPP-LI, insulin, and glucagon in the cell extract was also determined. Mean +/- SE IAPP-LI in the incubation medium increased from 0.041 +/- 0.003 pmol in 1.67 mM glucose to 0.168 +/- 0.029 pmol in 16.7 mM glucose (P less than 0.05) and 1.02 +/- 0.06 pmol in 16.7 mM glucose plus arginine and IBMX (P less than 0.05 vs. 1.67 or 16.7 mM glucose). Insulin secretion increased similarly from 4.34 +/- 0.27 to 20.2 +/- 0.6 pmol (P less than 0.05) and then to 135 +/- 5 pmol (P less than 0.05 vs. 1.67 or 16.7 mM glucose). Glucagon release tended to decrease with the increase in glucose concentration (0.39 +/- 0.01 vs. 0.33 +/- 0.02 pmol, P less than 0.1), whereas with the addition of arginine and IBMX to high glucose, glucagon release increased to 1.32 +/- 0.03 pmol (P less than 0.05 vs. 1.67 or 16.7 mM glucose).(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗
PubMed1990

A re-assessment of the regulation of adiposity and appetite by the brain insulin system.

We have provided strong support for the hypothesis that the pancreatic hormone, insulin, provides a signal to the brain indicating the level of adiposity. Because insulin is found in the cerebrospinal fluid (CSF) in direct proportion to plasma levels, and because changes of plasma insulin result in subsequent changes of CSF insulin, we previously hypothesized that the blood-borne insulin signal enters the central nervous system by initially entering the CSF and then diffuses into the brain. Such a route explained the time lag for influences of insulin upon food intake and body weight. Recent evidence suggests that insulin may enter the brain directly through brain capillaries, raising the possibility that what is measured in the CSF may not be indicative of insulin on its way into critical brain areas. Implications of this change of route of entry of insulin into the brain for the regulation of food intake and body weight are discussed.

Adipose Tissue↗
PubMed1990

Postanesthesia care unit extubation protocol based on the Marker Model.

In an attempt to clearly define nursing practice in the PACU, nurses and anesthesiologists worked collaboratively to develop an extubation protocol. The protocol is for patients no longer requiring mechanical ventilation and who will be extubated in the PACU. The protocol is unique in that it is written in a format derived from the Marker Model. Using a hierarchical concept, the Marker Model provides a framework for dividing nursing standards into three categories: structure, process, and outcome. While the extubation protocol illustrates an example of a process standard, the article also focuses on briefly describing the major components of the Marker Model and how they interrelate.

Clinical Protocols↗
PubMed1989

Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance.

To determine whether prolonged nicotinic acid (NA) administration produces insulin resistance and, if so, how the normal pancreatic islet adapts to prolonged insulin resistance, we administered incremental doses of NA to 11 normal men for 2 wk, ending at 2 g/day. Insulin sensitivity was measured with Bergman's minimal model. Islet function was evaluated by measurement of acute insulin (AIR) and glucagon (AGR) responses to arginine at three glucose levels. Insulin resistance was demonstrated and quantified by a marked drop in the insulin sensitivity index (Sl) from 6.72 +/- 0.77 to 2.47 +/- 0.36 x 10(-5) min-1/pM (P less than .0001) and resulted in a doubling of basal immunoreactive insulin levels (from 75 +/- 7 to 157 +/- 21 pM, P less than .001) with no change in fasting glucose (5.5 +/- 0.1 vs. 5.7 +/- 0.1 mM). Proinsulin levels also increased (from 9 +/- 1 to 15 +/- 2 pM, P less than .005), but the ratio of proinsulin to immunoreactive insulin did not change (12.7 +/- 1.9 vs. 10.3 +/- 1.9%). beta-Cell changes were characterized by increases in the AIR to glucose (from 548 +/- 157 to 829 +/- 157 pM, P less than .005) and in the AIR to arginine at the fasting glucose level (from 431 +/- 54 to 788 +/- 164 pM, P less than .05). At the maximal hyperglycemia level the AIR to arginine represents beta-cell secretory capacity, and this increased with administration of NA (from 2062 +/- 267 to 2630 +/- 363 pM, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Development and performance of a fully automated method for assay of C-reactive protein in the aca discrete clinical analyzer.

A quantitative immunoassay for C-reactive protein (CRP) has been developed for use in the Du Pont aca discrete clinical analyzer. Particle-enhanced turbidimetric immunoassay (PE-TIA) technology is used. The method has a CV of less than 10% in the range 2 to 120 mg/L. Neither hemolyzed samples (Hb less than 5 g/L), icteric samples (total bilirubin less than 300 mg/L), lipemic samples (triglyceride less than 15 g/L), nor some commonly used drugs interfere. Dithioerythritol is used to eliminate interference from rheumatoid factor. Good correlation was seen when the Du Pont CRP method was compared with the Beckman ICS, Syva EMIT, TDx, and Behring methods for CRP. The normal reference interval is 0 to 9 mg/L. The method, which is fully automated, is fast, requires only a few microliters of serum, and is well suited to emergency-room requirements.

Autoanalysis↗
PubMed1987

Cholesterol embolization syndrome. Occurrence after intravenous streptokinase therapy for myocardial infarction.

Two patients developed the cholesterol embolization syndrome after coronary angiography and intravenous streptokinase therapy for acute myocardial infarction. Clinical manifestations included cyanosis, ulcers, gangrene of the hands and feet, myalgias, intestinal infarction, eosinophilia, and renal failure. One patient died; one has survived with chronic renal failure. Streptokinase therapy may expose atheromatous plaques to the circulation by lysing platelet-fibrin thrombi.

Cholesterol↗