Lipemic plasma from normal and hyperlipemic patients has been fractionated on columns of 3% (w/v) aqueous polyvinylpyrrolidone (PVP) and the lipid composition of the separated fat particles (S(f) > 400) measured. Plasma from patients with carbohydrate-induced lipemia on fat-free diets contained particles with a greater percentage of cholesterol and phospholipid than either normal primary particles (which float to the top of 3% PVP columns) or secondary particles (which remain concentrated just above the plasma layer at the bottom of the 3% PVP column). These "hyperlipemia" particles remained in the lower half of 3% PVP columns, which allowed easy separation from primary (top) particles. In the same hypertriglyceridemic patients primary (top) particles with the usual lipid composition were isolated from plasma 8 hr after ingestion of 200 g of corn oil, but 24 hr after the meal, primary (top) particles isolated in the same way contained a higher percentage of cholesterol than normal primary particles. High-cholesterol primary (top) particles were isolated from the patients mentioned and also from patients with fat-induced lipemia after an overnight fast on a regular fat-containing diet. It is concluded that the lipid composition of primary particles is variable and reflects the length of time these particles have been in the general circulation.

Centrifugation↗

PubMed1966

A concept of the pathogenesis of diabetic lipemia.

Explore the source record for details and available documents.

Adult↗

PubMed1966

Use of constant composition polyvinylpyrrolidone columns to study the interaction of fat particles with plasma.

Fat particles (lipoproteins of S(f) > 400) have been obtained from dog and human lymph and from human post-alimentary plasma. They were flocculated by a solution of 5% polyvinylpyrrolidone (PVP) in 10% NaCl and layered at the bottom of tubes of PVP of various concentrations between 2% and 5% (w/v). As the concentration of PVP increased, a greater proportion of the particles accumulated at the top of the tube ("primary" particles). When the concentration of PVP in the tube was held constant at 3% PVP, dilution of the sample with plasma was found to produce an increased proportion of bottom particles ("secondary" particles). This observation suggests that bottom particles result from an interaction of top particles with plasma.

Animals↗

PubMedDate not supplied

Clinical importance of insulin secretion and its interaction with insulin resistance in the treatment of type 2 diabetes mellitus and its complications.

Type 2 diabetes primarily develops from pathogenic defects in the mechanisms of insulin secretion and hepatic and peripheral insulin action. The consequent disruption of normal glucose metabolism involves a number of organ systems and is ultimately manifested in fasting and daytime hyperglycemia. Chronically elevated blood glucose concentrations determine the progression of the disease by further exacerbating insulin resistance and causing beta-cell exhaustion in addition to decreasing their responsiveness to glucose. The beta-cell secretory dysfunction is characterized by the lack of the early phase of glucose-induced insulin secretion and the insufficient and delayed late phase of secretion. Glycemic levels in patients with type 2 diabetes are directly related to the risk of developing microvascular and macrovascular complications, the main cause of the morbidity and mortality associated with this disease. The goal of treatment is to decrease the risk and delay the progression of these complications by improving glycemic control. Current oral antidiabetic agents, used as monotherapy or in combination, include traditional insulin secretagogues, insulin sensitizers and inhibitors of carbohydrate absorption. A greater understanding of the pathophysiology of type 2 diabetes and recent findings on the significance of meal-related glycemia to overall glycemic control are expanding the therapeutic options for treating this disease.

Blood Glucose↗

PubMedDate not supplied

Bombesin stimulates insulin secretion and reduces food intake in the baboon.

Baboons received a 5-minute intravenous infusion of either saline or bombesin (BBS; 1-4 micrograms/kg) following 3 1/2 or 16 1/2 hours of food deprivation and were then allowed to eat for 30 minutes. Plasma insulin was significantly elevated following five minutes of BBS infusion, but there was no change of plasma glucose over the same interval. Bombesin infusion resulted in a dose-dependent decrease of food intake that was independent of deprivation time. Plasma insulin levels following the 30-minute meal were significantly depressed after BBS infusions such that there was essentially no change of plasma insulin over the duration of the meal, even though the baboons did not totally suppress their food intake. Following 3 1/2 hours food deprivation, BBS suppressed the post-prandial rise of plasma glucose in a dose-dependent manner. The results provide further evidence that BBS and/or structurally-related peptides are involved in the regulation of feeding and metabolism.

Animals↗

PubMedDate not supplied

Brain insulin binding is decreased in Wistar Kyoto rats carrying the 'fa' gene.

We have previously reported that insulin binding is decreased in the olfactory bulb of both heterozygous (Fa/fa) and obese (fa/fa) Zucker rats. In the present study, we measured insulin binding in membranes prepared from the olfactory bulb, cerebral cortex, and hypothalamus of control (Fa/Fa) Wistar Kyoto rats; "fatty" (fa/fa) Wistar Kyoto rats; and phenotypically lean (Fa/?) Wistar Kyoto rats. Insulin binding was decreased in all brain regions, as well as the liver of the obese Wistar Kyoto fa/fa rats. Additionally, insulin binding was decreased in the liver and brain membranes from the Fa/? Wistar Kyoto rats. As most of the Fa/? rats were probably carriers of one 'fa' gene, but the population was only slightly hyperinsulinemic, we conclude that--as in the Zucker rat--it is the presence and expression of the 'fa' gene rather than downregulation which results in the decreased insulin binding. Thus, regulation of the brain insulin receptor appears to be independent of plasma or cerebrospinal fluid insulin levels.

Animals↗

PubMedDate not supplied

Effect of CCK-8 on basal and meal-stimulated somatostatin in the baboon.

We measured the ability of CCK-8 alone, a test meal alone, or a combination of the two, to increase peripheral plasma somatostatin levels in the baboon. Baboons received a five-minute intravenous infusion of either CCK-8 (1, 2, or 4 micrograms/kg) or saline prior to a 30-minute meal. CCK-8 administration at all doses resulted in a significant rise of plasma somatostatin-like immunoreactivity (SLI). In addition, ingestion of a meal following a control saline infusion resulted in a significant rise of plasma SLI. However, the meal-related rise in SLI was blunted by prior administration of CCK-8 at all doses, including a dose which did not significantly decrease meal size. CCK-8 administration at all doses also blunted the meal-related rise of plasma insulin and glucose. We conclude that the known ability of CCK-8 to inhibit gastric emptying, as well as to decrease meal size, may account for its suppression of the meal-related SLI release.

Animals↗

PubMedDate not supplied

Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats.

In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals.

Animals↗

PubMedDate not supplied

Sensitivity of R-R variation and Valsalva ratio in assessment of cardiovascular diabetic autonomic neuropathy.

R-R variation and the Valsalva ratio are commonly used to quantitatively assess diabetic autonomic neuropathy (DAN). To assess the sensitivity of these two measures to parasympathetic ablation, 12 nondiabetic subjects were tested before and after graded doses (0.3-4.0 mg i.v.) of atropine. R-R variation was significantly reduced at 0.7 mg, whereas Valsalva ratio was not significantly smaller until the 2.0-mg dose of atropine. R-R variation continued to become progressively smaller during the 0.85-, 1.0-, and 2.0-mg doses. Valsalva ratio, but not R-R variation, was further reduced by the 4.0-mg dose. To further compare these two measures, two groups of diabetic subjects were compared with a group of nondiabetic subjects (n = 22). One group of diabetic subjects had symptoms of DAN (n = 22), and the other diabetic group had no symptoms of DAN (n = 19). In DAN subjects, both R-R variation (nondiabetic 33.2 +/- 4.3 vs. DAN 9.8 +/- 1.2, P less than .001) and the Valsalva ratio (nondiabetic 1.98 +/- 0.07 vs. DAN 1.55 +/- 0.07, P less than .001) were reduced. However, in asymptomatic subjects, R-R variation (23.2 +/- 3.9, P less than .05), but not Valsalva ratio (1.94 +/- 0.13, NS), was less than nondiabetic subjects. Even after beta-blockade, R-R variation was still less in both groups of diabetic subjects (nondiabetic 34.4 +/- 4.2 vs. DAN 7.4 +/- 1.3, P less than .001; asymptomatic 21.8 +/- 3.3, P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Quantitative evaluation of sympathetic and parasympathetic control of iris function.

The use of quantitative measurements of pupil size as an index of autonomic nervous system (ANS) activity in normal and diabetic subjects is described. The dual innervation of the iris by the parasympathetic (PNS) and sympathetic (SNS) nervous system was demonstrated by measurement of steady-state pupil size before and after changes in ANS activity by pharmacologic agents. In the presence of total PNS blockade, dark-adapted pupil size was a reliable index of SNS activity to the iris. Latency time (time from light stimulation to initial pupil response) appeared to be a good index of PNS activity. However, increased SNS activity may also prolong the latency time. Thus, consideration of SNS activity is necessary when evaluating the latency time. In 25 diabetic subjects, there was evidence of impaired SNS activity (smaller dark-adapted pupil size during total PNS blockade) and PNS activity (prolonged latency time). In a subgroup of diabetic subjects without clinical manifestations of autonomic neuropathy and normal subjects, both dark-adapted pupil size during PNS blockade (SNS index) and latency time (PNS index) were abnormal. The coefficient of variation for these two indices was less than 5% in glycemic stable diabetic subjects. Thus, these two indices are reliable and sensitive measures of the SNS and PNS activity to the iris in normal and diabetic subjects.

Adult↗

PubMedDate not supplied

Glycosylated hemoglobin and fasting plasma glucose in the assessment of outpatient glycemic control in NIDDM.

Interpreting measurements of fasting plasma glucose (FPG) and glycosylated hemoglobin (GHb) is subject to inherent limitations. The time course of change in GHb cannot be reliably specified in the individual patient, nor do single measurements of GHb convey any information regarding recent change or stability in glycemic control. To evaluate whether the clinical utility of these measurements may be extended, sequential measurements of FPG and GHb were examined from 16 outpatients with NIDDM followed over periods of 12 successive weeks or longer, including intervals following cessation of prior therapy or initiation of new hypoglycemic therapy with glipizide. In some individuals as well as groups of patients, changes in GHb followed patterns previously described by mean changes among groups of patients. Differing from those patterns, however, other individuals demonstrated prompt improvement in GHb following substantial improvement in FPG, confirming that patterns of change described from group means do not apply to all circumstances of changing glycemic control, though they may represent the most common. By using measurements of both FPG and GHb obtained on a single occasion to calculate a third parameter, called the glycosylated hemoglobin index (GHb-1), accurate information could be obtained regarding changes in glycemic control which occurred over intervals of 1-4 wk prior to the measurements. By this approach the utility of GHb measurements in the management of outpatients with NIDDM may be extended beyond retrospective description of the "average" prior metabolic control to include assessment of recent changes in glycemia, either deterioration or improvement.

Aged↗

PubMedDate not supplied

Autonomic neural dysfunction in recently diagnosed diabetic subjects.

Because onset of autonomic neural dysfunction in the diabetic syndrome has not been well established, sensitive and quantitative measures of autonomic nervous system (ANS) function were made in 19 non-insulin-dependent (NIDD) and 14 insulin-dependent (IDD) recent-onset diabetic subjects. The known duration of diabetes mellitus in the NIDD subjects was less than or equal to 12 mo. The duration in the IDD subjects was less than or equal to 24 mo. RR-variation during beta adrenergic blockade (an index of an ANS reflex involving the cardiac parasympathetic nervous system [PNS] pathway) was smaller than that of control subjects in both NIDD (P less than 0.001) and IDD subjects (P less than 0.01). This PNS abnormality was not likely to be due to volume depletion since acute volume depletion induced by furosemide in six normal subjects (1608 +/- 105 ml, mean +/- SEM) did not change RR-variation. Dark-adapted pupil size after topical PNS blockade (an index of iris sympathetic nervous system [SNS] activity) was also smaller in both groups of diabetic subjects (NIDD, P less than 0.01; IDD, P less than 0.05). Pupillary latency time (an index of an ANS reflex involving iris PNS pathway) was prolonged in the NIDD subjects (P less than 0.005) but was not significantly altered in the IDD subjects. Thus, it would appear that the ANS is impaired soon after the diagnosis of diabetes mellitus. We hypothesize that early impairment of the ANS is common in IDD and NIDD subjects. This finding is consistent with the hypothesis that abnormal carbohydrate metabolism is an important factor in the etiology of diabetic autonomic neuropathy.

Adult↗