Glucose transport and metabolism in adipocytes from newly diagnosed untreated insulin-dependent diabetics. Severely impaired basal and postinsulin binding activities.

Previous studies have shown cellular insulin resistance in conventionally treated insulin-dependent diabetics. To determine whether insulin resistance is also present in insulin-dependent diabetics before the commencement of insulin therapy, we studied nine newly diagnosed untreated insulin-dependent diabetics and nine control subjects. Insulin binding to adipocytes, monocytes, and erythrocytes was normal in the diabetic individuals. Basal (noninsulin stimulated) glucose transport rate was normal, whereas the maximal insulin responsiveness of glucose transport was severely impaired (P less than 0.02). Insulin sensitivity as judged by left or rightward shifts in the insulin dose-response curves was unchanged. Moreover, the basal lipogenesis rate measured at a glucose concentration of 0.5 mmol/liter was decreased in the diabetics (P less than 0.05), and the maximal insulin responsiveness of lipogenesis was also reduced (P less than 0.05). We conclude that fat cells from untreated insulin-deficient diabetics are insulin resistant. The major defects are (1) reduced maximal insulin responsiveness of glucose transport and conversion to lipids that are postbinding abnormalities, and (2) reduced basal glucose conversion to lipids.

The porcine acute phase protein response to acute clinical and subclinical experimental infection with Streptococcus suis.

The pig acute phase protein (APP) response to experimental Streptococcus suis (S. suis) infection was mapped by the measurement of the positive APPs C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp) and major acute phase protein (pig-MAP) and the negative APPs albumin and apolipoprotein (Apo) A-I. The aim was to elucidate the differences in the acute phase behaviour of the individual APPs during a typical bacterial septicaemic infection. Pigs were inoculated subcutaneously with live S. suis serotype 2 and blood was sampled before and on various days post inoculation (p.i.), until the pigs were killed and autopsied on day 14 p.i. Clinical signs (fever and lameness) were observed in four of the five inoculated pigs from day 2 p.i., and these pigs also had arthritic lesions at autopsy. CRP and SAA showed fast increases in serum concentrations, CRP being elevated from days 1 to 12 p.i. and peaking at 10 times the day 0-levels on day 1 p.i. SAA rose quickly to peak levels of 30-40 times the day 0-level on days 1-2 and returned to pre-inoculation level on day 5 p.i. Hp and pig-MAP showed slightly slower responses, both peaking around 5 days p.i. Hp was increased throughout the experiment with maximum levels around 10 times the day 0-levels, and pig-MAP was elevated on days 1-12 p.i. with peak levels of around seven times the day 0-levels. Apo A-I was decreased from days 1 to 8 and showed minimum levels of about 40% of day 0-levels around 1-2 days p.i. No clear pattern of changes in albumin levels could be identified. One pig, showing clinical signs on day 2 only, also showed an APP response, although of a relatively short duration, whereas three pigs presenting clinical signs for several days had a more protracted acute phase response. Remarkably, the one pig showing no clinical signs and no arthritic lesions showed an APP response comparable to that of the other, clinically affected pigs. Thus, both acute clinical and subclinical S. suis infection could be revealed by the measurement of one or more of the APPs CRP, SAA, Hp, pig-MAP and Apo A-I. The combined measurement of two or three APPs, including proteins with slow and fast kinetics, should be used to achieve the highest sensitivity for the detection of ongoing S. suis infection during a prolonged time period. A diagnostic tool based on such APP-measurements could considerably improve strategic control procedures for this important infection.

Effects of prostaglandin E2, indomethacin and adenosine deaminase on basal and insulin-stimulated glucose metabolism in human adipocytes.

The effects of prostaglandin E2 were studied on glucose metabolism (3-O-methylglucose transport, CO2 production and lipogenesis) in human adipocytes. Initially, the effects of endogenously produced adenosine and prostaglandins were indirectly demonstrated by using adenosine deaminase and indomethacin in the incubations. From these studies it was found that adenosine deaminase (5 micrograms/ml) had a pronounced effect on adipocyte glucose metabolism in vitro. In the basal (nonhormonal-stimulated) state, glucose transport, CO2 production and lipogenesis were inhibited by about 30% (P less than 0.05). Furthermore, adenosine deaminase significantly inhibited the isoproterenol- and insulin-stimulated CO2 production and lipogenesis (P less than 0.01). Indomethacin (50 microM) had a consistently inhibitory effect on the insulin-stimulated CO2 production (P less than 0.05), whereas indomethacin had no significant effects on basal or isoproterenol-stimulated glucose metabolism. In contrast to the relatively minor effect of endogenous prostaglandins, the addition of exogenous prostaglandin E2 significantly stimulated the glucose transport, glucose oxidation and lipogenesis in human adipocytes, especially in the presence of adenosine deaminase. Half-maximal stimulation was obtained at prostaglandin E2 concentrations of 2.2, 0.8 and 0.8 nM, respectively. The effect of prostaglandin E2 was specific, since the structurally related prostaglandin, prostaglandin F2 alpha, had practically no effect on glucose metabolism. The maximal effect of prostaglandin E2 (1 microM) on glucose metabolism was 30-35% of the maximal insulin (1 nM) effect. When insulin and prostaglandin E2 were added together, the effect of prostaglandin E2 on glucose metabolism was additive at all insulin concentrations tested.

Postreceptor effects of sulfonylurea on skeletal muscle glycogen synthase activity in type II diabetic patients.

To elucidate the subcellular mechanism of action of sulfonylurea on glucose utilization of skeletal muscle, we studied nine newly diagnosed patients with type II (non-insulin-dependent) diabetes. Examinations were performed before and after 8 wk of gliclazide therapy. Gliclazide treatment was associated with improved glycemic control and enhanced pancreatic beta-cell responses to meal stimulation. During euglycemic insulin clamps, insulin-inhibited endogenous glucose production was improved after gliclazide therapy. Moreover, mean (+/- SE) glucose disposal rate increased from 3.2 +/- 0.7 to 4.8 +/- 0.8 and from 7.9 +/- 0.9 to 10.4 +/- 0.9 mg.kg-1.min-1 at in vivo plasma insulin levels of approximately 75 and approximately 320 mU/L, respectively. In addition, insulin-receptor function and glycogen synthase activity were analyzed in skeletal muscle biopsies obtained in seven patients. The biopsies were obtained during basal insulinemia and hyperinsulinemia (approximately 320 mU/L) before and after treatment. Insulin receptors purified with wheatgerm agglutinin showed unchanged insulin-binding properties and unchanged receptor kinase function with respect to basal and insulin-stimulated phosphorylation of exogenous peptide poly(Glu80Tyr20). Gliclazide treatment had no effect on the maximal activities of glycogen synthase. Moreover, in biopsies obtained at basal insulinemia, the half-maximal activation constant for glucose 6-phosphate (A0.5) was identical before and after therapy (0.54 +/- 0.05 vs. 0.54 +/- 0.05 mM, respectively, NS). However, in biopsies obtained at hyperinsulinemia, A0.5 was 0.30 +/- 0.05 vs. 0.20 +/- 0.02 mM before and after gliclazide therapy, P less than .04.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved in vivo insulin effect during continuous subcutaneous insulin infusion in patients with IDDM.

It has recently been shown that conventionally treated IDDMs are insulin resistant. Using the insulin clamp technique, we studied the influence of metabolic status on the in vivo insulin effect in these patients. Eleven IDDMs, treated conventionally with diet and insulin for 10.7 +/- 5.6 yr, were studied before and after continuous subcutaneous insulin infusion (CSII) treatment (with a portable pump) for 6 mo. We found that conventionally treated diabetic subjects were extremely insulin resistant with regard to peripheral glucose uptake. Glucose uptake, at an insulin concentration of about 80 microU/ml, was 4.3 +/- 2.0 mg/kg X min before treatment compared with 11.5 +/- 4.0 mg/kg X min in normals (P less than 0.01). After pump treatment for 6 mo, metabolic control improved significantly (HbA1c decreased from 8.9 +/- 1.9% to 7.4 +/- 1.2%, P less than 0.01) and, parallel to that, glucose uptake increased about 80% to 7.5 +/- 3.5 mg/kg X min (P less than 0.01). The mean daily plasma FFA level decreased from 0.32 +/- 0.10 mmol/L to 0.21 +/- 0.07 mmol/L (P less than 0.01); this variable was negatively correlated to the glucose clearance rate (r = -0.62, P less than 0.01). There was no statistically significant change in mean daily plasma insulin and plasma growth hormone levels or in 24-h cortisol excretion in the urine (P greater than 0.1). The insulin binding capacity of serum IgG was also unchanged, and there was no significant relationship between this quantity and glucose clearance rates (r = 0.18, P greater than 0.1). We conclude that conventionally treated IDDMs are insulin resistant with regard to peripheral glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of post-segregational killing: secondary structure analysis of the entire Hok mRNA from plasmid R1 suggests a fold-back structure that prevents translation and antisense RNA binding.

The hok/sok system of plasmid R1 mediates plasmid stabilization by killing of plasmid-free cells. The Hok mRNA is very stable and can be translated into Hok killer protein. Translation of the Hok mRNA is inhibited by the small unstable Sok antisense RNA. Translation of hok is coupled to an overlapping reading frame termed mok. Translation of mok is tightly regulated by Sok RNA, and Sok RNA thus regulates hok translation indirectly through mok. The rapid decay of Sok RNA explains the onset of Hok synthesis in newborn plasmid-free segregants. However, a second control level is superimposed on this simple induction scheme, since the full-length Hok mRNA was found to be translationally inactive whereas a 3'-end truncated version of it was active. We have therefore previously suggested, that the 3'-terminal region of the full-length Hok mRNA encodes an element which prevents its translation. This element was termed fbi (fold-back inhibition). Here we describe the in vitro secondary structure of the entire Hok mRNA. Our results suggest a closed structure in which the 3'-end of the full-length Hok mRNA folds back onto the translational initiation region of mok. This structure explains why full-length Hok mRNA is translationally silent. The proposed structure was further supported by results obtained using mutations in the 3'-end fbi element. These "structure closing" mutations affected the structure much further upstream in the mok translational initiation region and concomitantly prevented antisense RNA binding to the same region of the mRNA. These results lend further support to the induction model that explains onset of Hok mRNA translation in plasmid-free segregants. The most important regulatory element in this model is the FBI structure formed between the 3'-end and the mok translational initiation region. This structure renders Hok mRNA translationally inactive and prevents antisense RNA binding, thus allowing the accumulation of a pool of mRNA which, by slow 3'-end processing, is activated in plasmid-free segregants, eventually leading to the elimination of these cells.

Adipocyte insulin binding and action in moderately obese NIDDM patients after dietary control of plasma glucose: reversal of postbinding abnormalities.

Studies of fat cells from patients with newly diagnosed, untreated non-insulin-dependent diabetes mellitus (NIDDM) have revealed severe abnormalities in insulin action on glucose transport and metabolism. To determine whether these defects can be reversed if good glycemic control is reached by dietary treatment, eight moderately obese NIDDM subjects were studied at diagnosis and again when the patients had been in good glycemic control induced by low-energy dieting for at least 2 mo (absence of glycosuria and fasting plasma glucose less than 7 mM). Average body weight decreased by 8 kg (P less than .05). Fasting plasma glucose decreased from 11.5 +/- 1.2 to 6.9 +/- 0.9 mM, whereas fasting serum insulin concentrations were unchanged. Adipocyte insulin binding at tracer concentration (15 pM, 37 degrees C) was not changed significantly (1.94 +/- 0.52 to 2.05 +/- 0.62% per 30 cm2 surface area/ml). The basal (non-insulin-stimulated) glucose transport (tracer glucose concentration 5 microM) increased from 25 +/- 12 to 44 +/- 14 pmol X 90 min-1 X 10 cm-2 surface area (P less than .02). The maximally insulin-stimulated glucose transport rate increased from 35 +/- 20 to 78 +/- 26 pmol/90 min (P less than .01). The percentage insulin response above basal levels increased from 31 +/- 40 to 89 +/- 58% (P less than .01). The insulin sensitivity (half-maximally stimulating insulin concentrations) was also improved (P less than .05). Glucose conversion rates to total lipids increased 34 +/- 62 and 65 +/- 80% in basal cells and maximally insulin-stimulated cells, respectively (.2 greater than P greater than .1, .1 greater than P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Classification of newly diagnosed diabetic patients as insulin-requiring or non-insulin-requiring based on clinical and biochemical variables.

In a prospective study of 41 consecutively referred newly diagnosed diabetic patients, we evaluated the predictive value of fasting and glucagon-stimulated C-peptide values, ketonuria, age, and body weight in the classification of subjects as insulin-requiring (IR) or non-insulin-requiring (NIR). The patients were followed up for greater than or equal to 12 mo and classified as NIR if adequate glycemic control could be achieved without insulin (i.e., fasting plasma glucose less than 8 mM and no glycosuria). Patients who needed insulin to obtain this status were classified as IR. We found that all subjects with plasma C-peptide values greater than 0.60 nM 6 min after intravenous glucagon were NIR, whereas all IR subjects together with 3 NIR subjects had C-peptide values below this limit. All NIR subjects but 1 had fasting C-peptide values greater than 0.30 nM, and all IR subjects but 1 had C-peptide values below this limit. Seventy-five percent of the subjects could be correctly classified by use of age and percent desirable body weight. Thus, all subjects greater than 40 yr old and greater than 100% ideal body weight were NIR, and all subjects below both these limits were IR. Ketonuria was found in 10 of 12 IR subjects and in 10 of 29 NIR subjects. We conclude that 1) 75% of the subjects could be correctly classified by use of age and percent desirable body weight only and 2) C-peptide measurements are useful in the classification of newly diagnosed diabetes, whereas presence of ketonuria is of limited value.

Sulfonylureas improve insulin binding and insulin action in non-insulin-dependent diabetes mellitus.

Sulfonylureas reduce plasma glucose concentrations in most patients with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism of this action is controversial. In this article we examine the issue of the peripheral effect of these drugs, i.e., the effect on insulin receptors and insulin action. In our studies we have found that sulfonylureas possess a selective regulatory in vivo effect on the cellular insulin binding to monocytes, independent of the diet and changes in plasma glucose and insulin concentrations. Furthermore, we found in in vitro studies that sulfonylureas affect the insulin receptors in a direct way. Thus, insulin binding to monocytes was increased during sulfonylurea treatment in both normal volunteers and patients with NIDDM. On the other hand, sulfonylureas seem to improve insulin action in NIDDM patients only. We conclude that the increased insulin binding in patients with NIDDM, induced by sulfonylurea treatment, may be of importance for the improved insulin action found in these patients. However, this hypothesis has to be proved.

Reduced binding and antilipolytic effect of prostaglandin E2 in adipocytes from patients with hyperthyroidism.

The present study was undertaken to evaluate the effect of thyroid hormones on prostaglandin E2 (PGE2) binding and action in human adipocytes. The study consisted of 12 patients with hyperthyroidism and 20 normal subjects. In adipocytes from hyperthyroid patients, there was a 32% decrease in [3H]PGE2-binding sites (P less than 0.01). This reduced binding was accompanied by a 46% reduction in the relative antilipolytic effect of PGE2 in adipocytes from patients with hyperthyroidism. These changes might, then, account for some of the enhanced lipolysis that occurs in hyperthyroid patients. Thyroid hormones significantly increased the lipolytic effect of isoproterenol (P less than 0.01). However, the lipolytic effect of theophylline plus adenosine deaminase and basal lipolysis also were increased in adipocytes from hyperthyroid subjects. The latter findings indicate that thyroid hormones induce a state of increased activation of lipolysis under both basal and stimulated conditions. It is concluded that thyroid hormones reduce the binding and action of PGE2 in human adipocytes, possibly via a cAMP dependent mechanism. These alterations will contribute to accelerated lipid metabolism in the hyperthyroid state.

Effect of fish-oil-enriched margarine on plasma lipids, low-density-lipoprotein particle composition, size, and susceptibility to oxidation.

We investigated the effect of incorporating n-3 polyunsaturated fatty acids (PUFAs) into the diet on the lipid-class composition of LDLs, their size, and their susceptibility to oxidation. Forty-seven healthy volunteers incorporated 30 g sunflower-oil (SO) margarine/d into their habitual diet during a 3-wk run-in period and then used either SO or a fish-oil-enriched sunflower oil (FO) margarine for the following 4 wk. Plasma concentrations of total cholesterol, triacylglycerols, HDL cholesterol, LDL cholesterol, and apolipoproteins A-I and B did not differ significantly between the groups during intervention. The FO margarine increased the concentration of n-3 very-long-chain PUFAs in the LDL particles, showing 93% (P < or = 0.0001), 8% (P = 0.05), and 35% (P = < 0.0001) increases in eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid, respectively, in the FO group compared with 3%, 7%, and 7%, respectively, in the SO group during the intervention. The cholesterol content of the LDL particles increased in the FO group [total cholesterol: 6% (P = 0.008); cholesterol ester: 12% (P = 0.014)], although it was not significantly different from that in the control group, whereas the other lipid classes and the size of the LDL particles remained unchanged in both groups. A reduction in the alpha-tocopherol content in LDL (6%, P = 0.005) was observed in the FO group. Ex vivo oxidation of LDL induced with Cu2+ showed a significantly reduced lag time (from 91 to 86 min, P = 0.003) and lower maximum rate of oxidation (from 10.5 to 10.2 nmol x mg(-1) x min(-1), P = 0.003) after intake of the FO margarine. The results indicate that consumption of the FO compared with the SO margarine had no effect on LDL size and lipid composition and led to minor changes in LDL a-tocopherol content and oxidation resistance.

Effects of perindopril on insulin sensitivity and plasma lipid profile in hypertensive non-insulin-dependent diabetic patients.

About 40% of patients with non-insulin-dependent diabetes (NIDDM) have hypertension, which in turn may contribute to their enhanced risk for cardiovascular diseases. However, a number of antihypertensive agents tend to cause a deterioration in the control of diabetes. The present study was designed to elucidate whether treatment with perindopril (a new angiotensin-converting enzyme [ACE] inhibitor) affects plasma lipid metabolism, glucose homeostasis, and insulin sensitivity. Ten patients with NIDDM and moderate hypertension were studied in a double-blind, placebo-controlled, crossover study encompassing 6 weeks of placebo treatment and 6 weeks of perindopril treatment given in random order. Mean systolic/diastolic blood pressure was 162/94 +/- 6/3 mm Hg during placebo treatment versus 157/91 +/- 5/2 mm Hg during perindopril therapy. Plasma levels of free fatty acids, triglycerides, high density lipoprotein (HDL) cholesterol, and total cholesterol were similar during placebo and perindopril treatment. Oral glucose tolerance tests showed similar responses of plasma glucose, serum insulin, and serum C peptide following placebo and perindopril treatment. Insulin sensitivity estimated with an intravenous insulin tolerance test (IVITT) was unchanged by perindopril therapy (KIVITT: 0.014 +/- 0.001 min-1 [placebo] versus 0.015 +/- 0.003 min-1 [perindopril], difference not significant. In conclusion, treatment with perindopril in NIDDM patients had no adverse effects on plasma lipids, glucose tolerance, or insulin sensitivity.

Alpha 2- and beta-adrenergic receptor binding and action in gluteal adipocytes from patients with hypothyroidism and hyperthyroidism.

The alpha 2- and beta-adrenergic receptor activities have been investigated in human adipocytes in relation to thyroid status. Adipocytes from 11 hypothyroid and 18 hyperthyroid were compared with 19 euthyroid (normal) subjects. The lipolytic and cAMP responses to isoproterenol and epinephrine were greatly enhanced in adipocytes from hyperthyroid subjects (P less than .01) and impaired in adipocytes from hypothyroid subjects (P less than .05). However, the antilipolytic effect of clonidine (alpha 2-agonist) and the effect of clonidine on cAMP were similar in all three groups. The alpha 2- and beta-receptor numbers were both slightly increased in hyperthyroidism, but the ratio between the alpha 2- and beta-receptors was unchanged in relation to normal subjects. On the other hand, the adrenergic binding to adipocyte membranes from hypothyroid subjects was reduced, and the beta-receptor binding was reduced even much more (50%) than the alpha 2-receptor binding (20%, P less than .01). Thus, the alpha 2- and beta-receptor ratio was almost doubled in hypothyroid adipocytes (P less than .01). The antagonist affinity against the adrenergic receptors (determined by propranolol and yohimbine, respectively) was unchanged in the three groups. Agonist binding determined in intact adipocytes revealed unaltered affinity of clonidine for the alpha 2-receptor in the three groups. In hyperthyroidism, though, there was enhanced affinity of isoproterenol in competition with the beta-receptor (P less than .05). It is concluded that the inhibitory alpha 2-receptor pathway functions normally in all groups, indicating that the alpha 2-receptors and the alpha 2-receptor-mediated pathway in human adipocytes are relatively unaffected by thyroid hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary changes on cellular insulin binding and in vivo insulin sensitivity.

The effect of a low-sucrose, low-fat diet on insulin sensitivity, insulin binding to monocytes, and insulin secretion in nonketotic diabetic patients was studied. Ten obese diabetics were studied for 1 yr before and during treatment with a 1200-1500-kcal diet, whereas six diabetics of normal weight were studied for 3 mo before and after treatment with a 2200-2400-kcal diet. In the obese group, no change was found in the insulin response to i.v. injection of glucose during treatment (p greater than 0.1), but the insulin sensitivity was normalized after 1 yr (p less than 0.01). The clinical normalization and the improvement of insulin sensitivity were accompanied by a parallel normalization of the binding of insulin to monocytes (p less than 0.01). In the group of normal-weight diabetics, both the insulin sensitivity (p less than 0.05) and the insulin binding to monocytes (p less than 0.05) were normalized after a 3-mo treatment period, but the insulin secretion increased (p less than 0.05) without reaching normal values. We conclude that most nonketotic diabetic patients can be controlled by diet treatment alone. The mechanism of action of the low-fat, low-sucrose diet seems for the greatest part to be a normalization of the insulin sensitivity, which is partly caused by a normalization of the cellular insulin binding.

Insulin receptor binding and insulin action in human fat cells: effects of obesity and fasting.

We have studied (125I)-insulin binding and insulin dose response relationships of (14C)-methylglucose transport conversion of (14C)-glucose to CO2 and total lipids, and lipolysis at 37 degrees C and pH 7.4 in adipocytes from obese patients before (n = 15) and after fasting for 10 days (n = 6). Studies of adipocytes from obese before fasting showed a significant reduction of insulin binding when expressed to cell surface area and rightward shifts of the insulin dose response curves (decreased insulin sensitivity) for glucose transport, glucose oxidation, lipogenesis and antilipolysis. The decreased insulin sensitivity of adipocytes from obese was most likely the functional consequence of the impaired insulin binding. Moreover, decreased maximal glucose transport capacities were present in rat cells from obese both in the basal and maximally insulin stimulated states. Similarly, the percentage response above basal level to maximal insulin stimulation of glucose oxidation and lipogenesis was impaired to these cells. The latter findings suggest post receptor defects localized both to the transport system per se and to intracellular mechanisms involved in the metabolism of glucose. Conversely, the post receptor pathways for the insulin induced antilipolysis was intact in fat cells from obese man. Studies after fasting showed an increase of adipocyte insulin binding accompanied by an increased sensitivity to the antilipolytic effect of insulin with unchanged maximal responsiveness. However, due to marked post receptor alterations, the insulin stimulated glucose utilization was severely blunted. Thus, the glucose transport system of adipocytes from all fasted subjects was totally unresponsive to insulin, while some of the fasted patients had a slight response of glucose oxidation and lipogenesis in the presence of insulin in maximally effective concentrations.

Abdominal obesity is associated with insulin resistance and reduced glycogen synthetase activity in skeletal muscle.

Insulin resistance is commonly associated with obesity. The present study was performed to investigate the relative importance of total fat mass versus localization of adipose tissue in insulin-stimulated glucose disposal (Rd) and skeletal muscle glycogen synthase (GS) activity in obese individuals. Twenty obese women with an average body mass index (BMI) of 37.8 +/- 1.3 kg/m2 and a waist to hip ratio (WHR) ranging from 0.78 to 1.02 were examined during basal conditions and following hyperinsulinemia (hyperinsulinemic euglycemic clamp). To accurately determine body composition, the following three methods were used: anthropometric measurements, dual-energy x-ray absorptiometry scanning (DEXA-scan), and bioelectric impedance measurements. In addition, indirect calorimetry and muscle biopsy were performed. Insulin-stimulated glucose Rd was negatively correlated with WHR (R = -.52, P < .025) whereas there were no correlations with BMI or percent fat (R = .16, NS and R = .16, NS, respectively). Furthermore, a negative correlation between WHR and insulin stimulation of GS activity in skeletal muscle was found (R = -.62, P < .005). In contrast, BMI and percent fat were not correlated with the insulin effect on GS activity in skeletal muscle (R = .34, NS and R = -.35, NS, respectively). The concentration of nonesterified fatty acids (NEFA) during hyperinsulinemia was strongly correlated with WHR and abdominal localization of adipose tissue (determined by DEXA-scan; R = .60, P < .005 and R = .60, P < .007, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased insulin binding to adipocytes and monocytes and increased insulin sensitivity of glucose transport and metabolism in adipocytes from non-insulin-dependent diabetics after a low-fat/high-starch/high-fiber diet.

Nine non-insulin-dependent diabetics were studied before and after 3 weeks on an isoenergetic high-fiber/high-starch/low-fat diet (alternative diet), and nine non-insulin-dependent diabetics were studied on their usual diet. In the group that ate the alternative diet, the intake of fiber and starch increased 120% and 53%, whereas fat intake decreased 31%. Diabetes control improved as demonstrated by decreased fasting plasma glucose (P less than 0.05) and 24-hour urinary glucose excretion (P less than 0.05). The in vivo insulin action increased (KIVITT increased, P less than 0.05) with no change in fasting serum insulin levels. In fat cells obtained from patients in the alternative-diet group, insulin receptor binding increased (P less than 0.05) after the change of diet. Insulin binding to purified monocytes (more than 95% monocytes) also increased (P less than 0.05), whereas no change was found in insulin binding to erythrocytes. When lipogenesis was studied at a tracer glucose concentration at which glucose transport seems to be rate limiting, insulin sensitivity increased (P less than 0.02). This is the predicted consequence of increased receptor binding. Moreover, when CO2 production and lipogenesis were studied at a higher glucose concentration, where steps beyond transport seem to be rate limiting for glucose metabolism, increased insulin sensitivity was also observed. In contrast, no change was found in maximal insulin responsiveness. Fat and blood cells from the patients who continued on their usual diet showed no changes of the mentioned quantities.(ABSTRACT TRUNCATED AT 250 WORDS)

Early pathogenesis and inflammatory response in experimental bovine mastitis due to Streptococcus uberis.

A generally similar clinical response was observed in six lactating Holstein-Friesian cows after intramammary inoculation with approximately 10(7) colony-forming units of Streptococcus uberis. Increased concentrations of serum amyloid A (SAA) were measured in both milk and serum taken 6 and 11h after inoculation, respectively. In contrast, increased concentrations of haptoglobin were detected after 10h of infection, in milk only. In the blood, tumour necrosis factor-alpha (TFN-alpha) was detected (0.503 ng/ml) in only one animal, at the time of euthanasia (10h after infection). Interferon-gamma (IFN-gamma), like haptoglobin, was not detected in blood. Parallel to the development of inflammation and influx of inflammatory cells into the udder tissue, a marked decrease in the number of monocytes and neutrophils in blood was observed. Bacteria were found both intracellularly (macrophages and neutrophils) and within the lumen of ducts and alveoli. Lesions developed progressively in an ascending manner and became widespread throughout the mammary gland in less than 8h. The parallel development of inflammation and increased concentrations of SAA and haptoglobin in milk points to these acute phase proteins as potential diagnostic markers for the early detection of S. uberis -associated mastitis.

[Non-insulin-dependent diabetes mellitus. Diagnosis and treatment. An interpretation]. / Ikke-insulinkraevende diabetes mellitus. Diagnostik og behanding. En klaringsrapport.

There are approximately 100,000 non-insulin-dependent diabetics in the Danish population and the incidence appears to be increasing. As the disease is complicated by a series of arteriosclerotic manifestations together with hypertension and eye changes, it presents great problems in the primary and also in the secondary sector. The Danish Association for Internal Medicine has, on this basis, prepared an explanatory report with the main object of establishing guidelines for treatment of the disease both medically and by organisation. The report contains a review of the patho-physiological conditions with emphasis on resistance to insulin and the basic cellular defect. The connections with arteriosclerosis and hypertension are also emphasized. The significance of the diet in the treatment of the condition is also emphasized as approximately 80% of the patients are overweight. Guidelines for treatment with sulphonurea, biguanides and insulin are presented. In order to provide optimal treatment and control of non-insulin-dependent diabetics and to provide them a better quality of life closer cooperation between general practitioners and diabetic clinics is recommended. In particular, it appears to be desirable to involve diabetic clinics at the commencement of the disease when the need for training is great.