Lower Serum Glucose Research Articles

Hepatic gluconeogenesis and the activity of PDH in individual tissues of GTG-obese mice following adrenalectomy.

Adrenalectomy (ADX) lowers circulating glucose levels in animal models of non-insulin dependent diabetes (NIDDM) and obesity. To investigate the role of hepatic glucose production (HGP) and tissue glucose oxidation in the improvement in glucose tolerance, hepatocyte gluconeogenesis and the activity of pyruvate dehydrogenase (PDH) were examined in different tissues of gold thioglucose (GTG) obese mice 2 weeks after ADX or sham ADX. GTG-obese mice which had undergone ADX weighed significantly less than their adrenal intact counterparts (GTG ADX: 37.5 +/- 0.7 g; GTG: 44.1 +/- 0.4; p < 0.05), and demonstrated lower serum glucose (GTG ADX: 22.5 +/- 1.6 mmol/L; GTG: 29.4 +/- 1.9 mmol/L; p < 0.05) and serum insulin levels (GTG ADX: 76 +/- 10 microU/mL; GTG: 470 +/- 63 microU/mL; p < 0.05). Lactate conversion to glucose by hepatocytes isolated from ADX GTG mice was significantly reduced compared with that of hepatocytes from GTG mice (GTG ADX: 125 +/- 10 nmol glucose/10(6) cells; GTG: 403 +/- 65 nmol glucose/10(6) cells; p < 0.05). ADX also significantly reduced both the glycogen (GTG ADX: 165 +/- 27 mumol/liver; GTG: 614 +/- 60 mumol/liver; p < 0.05) and fatty acid content (GTG ADX: 101 +/- 9 mg fatty acid/g liver; GTG: 404 +/- 40 mg fatty acid/g liver; p < 0.05) of the liver of GTG-obese mice. ADX of GTG-obese mice reduced PDH activity by varying degrees in all tissues, except quadriceps muscle. These observations are consistent with an ADX induced decrease in hepatic lipid stores removing fatty acid-induced increases in gluconeogenesis and increased peripheral availability of fatty acids inhibiting PDH activity via the glucose/fatty acid cycle. It is also evident that the improvement in glucose tolerance which accompanies ADX of GTG-obese mice is not due to increased PDH activity resulting in enhanced peripheral glucose oxidation. Instead, it is more likely that reduced blood glucose levels after ADX of GTG-obese mice are the result of decreased gluconeogenesis in the liver.

Lipid and carbohydrate metabolic risk markers for coronary heart disease and blood pressure in healthy non-obese premenopausal women of different racial origins in the United Kingdom

Metabolic risk markers for coronary heart disease (CHD) were determined in apparently healthy females of differing racial origins residing in the United Kingdom. The females were of black (n = 122), Oriental (n = 114), South Asian (n = 128), and white (n = 271) origin, premenopausal, non-obese, and aged 16 to 45 years. In comparison to whites, South Asians had lower serum high-density lipoprotein (HDL) cholesterol and HDL 2 cholesterol and higher fasting and oral glucose tolerance test plasma insulin responses. Black females had higher fasting plasma and oral glucose tolerance test insulin and lower serum triglyceride and glucose compared with white females. Orientals differed from whites in having higher fasting and oral glucose tolerance test insulin concentrations. Resting systolic or diastolic blood pressures, total serum cholesterol, HDL 3 cholesterol, and low-density lipoprotein (LDL) cholesterol did not differ between groups. Whereas previous studies have demonstrated similar differences in representative samples from different ethnic communities, our results clearly demonstrate that differences also exist in young healthy females, individuals considered to have the least risk of CHD.

Effects of a Fat Substitute, Sucrose Polyester, on Food Intake, Body Composition, and Serum Factors in Lean and Obese Zucker Rats

Sucrose polyester, a fat substitute, has shown promise in reducing blood cholesterol and body weight of obese individuals. Effects of this compound in the Zucker rat, a genetic model of obesity, are unknown. Thus, we examined food intake, body weight, body composition, and several metabolic parameters in sera of lean and obese female Zucker rats. Eight-week-old lean and obese animals were given a choice between a control diet (15% corn oil) and fat substitute diet (5% corn oil and 10% sucrose polyester) for 2 days. Next, one-half of the lean and obese groups received control diet; the remaining lean and obese rats received fat substitute diet for 18 days. Cumulative food intake was depressed in fat substitute groups relative to control-fed animals; however, this effect was more predominant in obese animals. Obese rats consuming fat substitute diet (O-FS) gained less weight as compared to obese control-fed animals (O-C). Lean rats given fat substitute (L-FS) did not have significantly different body weights as compared to the L-C group. Fat substitute groups, combined, had lower body fat and higher body water as compared to controls. The O-FS group had lower serum glucose and insulin and higher fatty acid levels compared to the O-C group. There were no differences in serum cholesterol, HDL, or triglyceride levels due to fat substitute diet. These data suggest that the obese Zucker rat is unable to defend its body weight when dietary fat is replaced with sucrose polyester.

Insulin secretion in pancreatic islets from rats with cirrhosis

Cirrhosis was induced in rats by subcutaneous injections of CCl4 for 13 or 17 weeks. The morphology of the pancreatic islets from the CCl4-treated rats was found to be normal. The CCl4-treated rats had lower fasting serum glucose levels and higher serum insulin levels than the controls. After an oral glucose load (3 g/kg body weight), glucose levels in CCl4-treated rats stayed within the normal range, whereas the serum insulin levels remained higher with a delayed decline of insulin with time. In vitro perifusion of islets from the CCl4-treated rats showed that the response to 16.7 mmol/l glucose was reduced with both lower total insulin output and stimulated insulin output, whereas the patterns of first and second phase of insulin release did not differ. The insulin content of the perifused islets was not affected by 13 weeks of CCl4 treatment. Islets from rats treated with CCl4 for 17 weeks showed normal secretory response to 20 mmol/l L-arginine. Taken together, the results, showing normal or reduced capacity for insulin secretion, suggest that the hyperinsulinemia accompanying CCl4-induced cirrhosis is not due to increased secretion of the pancreatic islets. It may rather be associated with decreased insulin degradation by the liver with cirrhosis.

The calcium channel blocker amlodipine raises serum dehydroepiandrosterone sulfate and androstenedione, but lowers serum cortisol, in insulin-resistant obese and hypertensive men.

To determine whether the calcium channel blocker amlodipine improves glucose tolerance and alters serum adrenal androgen and glucocorticoid levels in insulin-resistant men, 24 obese and hypertensive men were enrolled into a single blind, placebo-controlled study. An amlodipine group (n = 12) and a placebo group (n = 12) were studied before and after treatment with either amlodipine (5 mg) or placebo capsule twice daily for 7 days by determining serum insulin, glucose, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and cortisol in the fasting state and during an oral glucose tolerance test. Amlodipine treatment 1) lowered fasting serum insulin (from 273 +/- 19 to 200 +/- 17 pmol/L; P < 0.0005) and glucose (from 5.4 +/- 0.1 to 5.1 +/- 0.1 mmol/L; P < 0.02), 2) reduced the area under the curve for glucose (from 1342 +/- 25 to 1198 +/- 23 mmol/L.min; P = 0.0001) and the area under the curve for insulin (from 155.5 +/- 7.8 to 103.9 +/- 4.3 nmol/L.min; P = 0.0001) during the oral glucose tolerance test, 3) increased fasting serum DHEA-S (from 5.19 +/- 0.37 to 7.95 +/- 0.58 mumol/L; P = 0.0001) and androstenedione (from 5.65 +/- 0.65 to 6.83 +/- 0.53 nmol/L; P < 0.01), and 4) decreased fasting serum cortisol (from 538 +/- 35 to 494 +/- 26 nmol/L; P < 0.05). Fasting serum androstenedione declined slightly in the placebo group (from 5.96 +/- 0.60 to 5.74 +/- 0.57 nmol/L; P < 0.005), but no change occurred in glucose tolerance, fasting serum DHEA-S, or cortisol. We conclude that amlodipine treatment improves glucose tolerance, reduces fasting and glucose-stimulated serum insulin levels, increases serum DHEA-S and androstenedione levels, and decreases circulating cortisol.

Endotoxin-induced fetal growth retardation in the pregnant guinea pig

Our purpose was to test the hypothesis that bacterial endotoxin may reduce fetal growth and to assess some of the pathophysiologic mechanisms of such an effect. Two randomly selected groups of nine guinea pigs at 30 days' gestation were treated with a solution of endotoxin isolated from Bacteroides fragilis or with solvent alone. Antibody titers, glucose, triglycerides, and 6-keto-prostaglandin F1 alpha were determined in maternal or fetal blood samples. Fetal weight was determined at 61 days' gestation. Endotoxin-treated guinea pigs showed positive antiendotoxin antibody titers, reduced weight gain, and significantly higher serum levels of triglycerides and 6-keto-prostaglandin F1 alpha, but not of glucose, than did sham-treated controls. Fetuses of endotoxin-treated animals had significantly lower birth weights and serum glucose concentrations and significantly higher triglyceride levels than did control fetuses. Bacteroides fragilis endotoxin causes fetal growth retardation in the pregnant guinea pig, which may be due to alterations in carbohydrate and fat metabolism mediated by cytokine action.

Asymmetric Septal Hypertrophy in Infants of Diabetic Mothers

Maternal hyperglycemia may result in fetal hyperinsulinemia and asymmetric septal hypertrophy, macrosomia, and hypoglycemia in infants of diabetic mothers. We monitored glycosylated hemoglobin levels in 61 pregnant diabetic women each trimester as an index of maternal glycemic control and did serial fetal echocardiograms starting at 18 weeks of gestation. At delivery, cord blood C-peptide levels were obtained as an index of fetal hyperinsulinemia. Infants were assessed for hypoglycemia, macrosomia and septal thickening by echocardiography. Nineteen of the 61 infants (31%) had septal hypertrophy, were heavier, and had higher cord blood C-peptide levels and lower serum glucose levels than unaffected infants. Maternal glycosylated hemoglobin levels were higher during the third trimester in mothers of affected infants. Our data support a possible relationship between third-trimester maternal hyperglycemia and neonatal asymmetric septal hypertrophy, macrosomia, and hypoglycemia.

Serum glucose and insulin responses to an insulin-containing ophthalmic solution administered topically in clinically normal cats

SUMMARY Serum glucose and immunoreactive insulin concentrations were monitored after topical administration of an insulin-containing ophthalmic solution in 20 clinically normal cats. Three ophthalmic surface-acting agents, benzalkonium chloride, dimethyl sulfoxide, and proparacaine hydrochloride, were evaluated individually for their effectiveness in enhancing absorption of topically applied insulin. The ophthalmic effects of insulin-containing ophthalmic preparations were assessed by complete ophthalmic examination before and at the conclusion of each test period. Withholding of food overnight (12 hours) preceded each topical application of insulin-containing ophthalmic solution (12.25 to 26.4 U/cat), either alone or in combination with surface-acting agents, after which blood samples were drawn serially from an indwelling iv catheter over a period of 8 hours. Baseline serum insulin concentration, after food was withheld for 12 hours, in nonstressed cats was 6.0 μU/ml (geometric mean), and an exponentiation of the logarithmic quantity (mean ± sd) yielded values of 1.5 to 23.0 μU/ml. All ophthalmic solutions tested failed to significantly lower serum glucose concentration or increase serum insulin concentration. Solutions used did not induce deleterious effect on ocular structures. Results indicate that topical administration of insulin-containing ophthalmic solution, either alone at the concentrations used or in combination with surfaceacting agents, did not result in effective absorption of insulin across the conjunctival and lacrimal nasal mucosa in biologically relevent quantities. Thus, this route of insulin administration, under these specific conditions, is not an effective alternative or adjunct to SC administration of insulin for treatment of cats with insulin-dependent diabetes mellitus or severe noninsulin-dependent diabetes mellitus.

Sucrose and Delinquency: Oral Sucrose Tolerance Test and Nutritional Assessment

Claims that juvenile delinquency may be associated with reactive hypoglycemia or nutritional deficiencies have received widespread attention but little objective evaluation. To assess the validity of these claims, nutritional and psychological indices of juvenile delinquents have been measured. Serum glucose and insulin profiles during an oral sucrose tolerance test were measured in 137 delinquent and 41 nondelinquent male adolescents aged 14 to 19. In addition, nutritional status of both populations was assessed by anthropometry (height, weight, arm circumference, triceps skin fold) and biochemical measures (hematocrit, red-blood cell thiamin, and serum copper, ferritin, and zinc). Delinquent subjects had slightly but significantly lower serum glucose values at four of six time points (fasting, 60 minutes, 120 minutes, 180 minutes) and higher serum insulin values at one time point (30 minutes) compared with nondelinquent subjects. Changes in glucose from fasting levels indicate that these subjects were regulating serum glucose adequately, but doing so at lower values; changes in insulin from fasting levels indicate that black delinquents initially secreted more insulin than either white subject group. There were no significant associations between excursions in serum glucose or insulin and any adrenergic signs or symptoms of low blood glucose levels. Nutritional status of incarcerated delinquents did not differ from that of nonincarcerated subjects on most measures. Although the significantly lower serum glucose levels and higher serum insulin levels are intriguing, no support is offered by results of this study for allegations that sucrose ingestion causes reactive hypoglycemia in juvenile delinquents or that delinquent male adolescents are at greater risk nutritionally than male adolescents of the same age who are not delinquent.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary status of Seventh-Day Adventist vegetarian and non-vegetarian elderly women

The purpose of this study was to investigate nutrient intakes of Seventh-Day Adventist elderly women who were similar in many demographic and life-style factors except for choice of diet. Twenty-three vegetarian and 14 non-vegetarian elderly women (mean +/- standard error ages 72.2 +/- 1.3 and 71.1 +/- 1.4 years, respectively) were recruited on the basis of several selection criteria, including race, religion, education, geographic area, Quetelet index, self-reported absence of major chronic disease and use of medications, and physical activity. Average years +/- SE of adherence to dietary regimens were 47.0 +/- 2.9 and 71.2 +/- 1.4 in the vegetarian and non-vegetarian groups, respectively. Results from analysis of 7-day food records showed that vegetarians consumed significantly less cholesterol, saturated fatty acids, and caffeine but more carbohydrate, dietary fiber, magnesium, vitamins E and A, thiamin, pantothenic acid, copper, and manganese than non-vegetarians (p less than .05). On the basis of group means, 67% of the Recommended Dietary Allowance was met for all nutrients except zinc and vitamin D in both groups, and vitamins B-6, folacin, and vitamin E in the non-vegetarians. Compared with non-vegetarians, vegetarians had significantly lower serum glucose (5.18 +/- 0.11 vs. 4.65 +/- 0.09 mmol/L), low-density-lipoprotein cholesterol (4.08 +/- 0.25 vs. 3.34 +/- 0.19 mmol/L), and total cholesterol levels (6.46 +/- 0.27 vs. 5.62 +/- 0.21 mmol/L) (p less than .05). In summary, when healthy elderly vegetarian women were compared with closely matched non-vegetarian peers, the vegetarian diet was associated with improved nutrient intake and associated reductions in blood glucose and lipid levels.

Effects of several simple sugars on serum glucose and serum fructose levels in normal and diabetic subjects

Fructose has a reaction constant 7.5 times as high as that of glucose in its nonenzymatic reaction with protein in vitro. The effects of glucose, sucrose and fructose ingestion on serum fructose and glucose levels were studied to evaluate the overall biohazard, i.e., the probability of their altering proteins while circulating in the blood. Normal and diabetic subjects were given either 75 g glucose, 75 g fructose, 75 g sucrose, or 112.5 g fructose after fasting, and their serum levels of sugars were measured at 0, 1, 2 and 3 h. In normal subjects, fructose ingestion produced significantly lower serum glucose levels and significantly higher serum fructose levels than did glucose ingestion, while sucrose produced intermediate results. The glycemic effect was found to be lowest for fructose and highest for glucose. The calculated overall biohazard was, however, highest for fructose and lowest for glucose in normal subjects. Furthermore, the serum fructosemic index was directly proportional to the amount of fructose ingested. In diabetic subjects, blood fructose clearance was significantly more delayed than in the controls when the same amount of fructose was ingested. These results suggest that an evaluation of the effects of simple in the diabetic diet requires a closer examination of the overall biological effects of the sugars.

Vitrification of mouse islets of Langerhans: Comparison with a more conventional freezing method

The possibility of cryopreservation of islets of Langerhans by vitrification using a mixture of cryoprotectants was investigated and the results were compared with a more conventional freezing method using Me 2SO as cryoprotectant. Isolated mouse islets were divided into three groups: (1) control islets cultured for 6 days, (2) islets which were cryopreserved by vitrification after 2 days of culture, and (3) islets frozen in 1.5 M Me 2SO after 2 days of culture. After warming, islets from groups 2 and 3 were cultured for 4 days. The thus treated islets were investigated with respect to insulin secretion in the presence of 2.5 or 25 m M glucose, survival during postwarming culture, morphology, and capability to reverse streptozotocin-induced diabetes. The insulin secretion in islets from all groups could be stimulated by a factor 5 or more by an increase in the concentration of glucose from 2.5 to 25 m M. The secretion of insulin in the presence of 2.5 m M glucose was similar in all groups of islets. The secretion of insulin in the presence of 25 m M glucose was slightly but not significantly lower in the cryopreserved islets than in the control noncryopreserved islets. The survival of islets during postwarming culture was comparable after cryopreservation with both methods, and islets from both groups could lower serum glucose in streptozotocin diabetic mice. We conclude that islets cryopreserved by the vitrification method are functional in vitro and in vivo. This method is quick, simple, and cheap because the use of complicated freezing equipment is avoided.

Effect of a hypoglycaemic agent M&B 39890A on glucagon secretion in isolated rat islets of Langerhans.

Administration of the compound M&B 39890A lowered serum glucose levels significantly (p less than 0.001) in genetically obese mice, while no effect on serum insulin levels was observed. In in vitro experiments with isolated rat islets of Langerhans M&B 39890A inhibited arginine-stimulated glucagon release at all concentrations tested (0.5, 5.0 and 50 mumol/l). Insulin secretion was not inhibited by M&B 39890A (0.5 and 5.0 mumol/l), but was slightly decreased at 50 mumol/l. M&B 39890A (5 mumol/l) also inhibited glucagon secretion in vitro in the presence of 2 mmol/l, 6 mmol/l and 20 mmol/l glucose, while exerting no effect on insulin secretion. These results suggest that the hypoglycaemic action of M&B 39890A may be due to its direct and selective effect on glucagon secretion; this appears to operate by a mechanism different to that of glucose.

Trials of rectal insulin suppositories in healthy humans

Administration of an insulin suppository containing adjuvant such as sodium salicylate and l-phenylalanine enamine ethylacetoacetate (enamine) to healthy male human subjects increased serum immunoreactive insulin (IRI) levels significantly. However, to decrease serum glucose concentrations significantly in humans, high serum IRI levels have to be maintained for at least about one hour in humans, rather than being transient. In comparison with enamine, sodium salicylate seems to be feasible as adjuvant in the insulin suppository since its administration to human subjects resulted in high IRI serum levels for a period long enough to lower serum glucose concentrations significantly.

Portal ν peripheral hyperinsulinemia and very low density lipoprotein triglyceride kinetics

The effect of subcutaneously delivered insulin on the kinetics of rat plasma triglycerides was compared to that of intraperitoneally delivered insulin. The former route delivered insulin primarily extrahepatically and the latter, intraportally. In comparison to the intraperitoneally delivered insulin, the subcutaneously delivered insulin was associated with a higher peripheral serum insulin, lower serum glucose, lower serum FFA, lower serum triglycerides, and similar rate of triglyceride secretion. The activity of adipose tissue lipoprotein lipase was directly related to the serum insulin concentration. The pattern of serum triglycerides and lipoprotein lipase in the rats receiving subcutaneous insulin suggested that their rate of triglyceride removal exceeded that seen in the rats receiving intraperitoneal insulin. These observations indicate that the route of insulin delivery can influence the balance between the hepatic and extrahepatic effects of insulin on triglyceride kinetics.

Hyperglycemia preserves brain mitochondrial respiration during anoxia.

We examined brain mitochondrial function in normo- (5 mM) and hyperglycemic (50 mM) cats after 8 min of anoxia. In anoxic normoglycemic cats, mitochondrial state 3 respiration with NAD-linked substrates glutamate or pyruvate (both plus malate) was inhibited 30-50%. The uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) maximally stimulated respiration, indicating that inhibition of phosphorylation, not impairment of electron transport, substrate transport, or oxidation was present. State 3 respiration with succinate (plus rotenone) was unaffected. Mitochondrial respiratory control ratios trended toward reductions whereas ADP/O ratios remained unchanged. In contrast, brain mitochondria from anoxic hyperglycemic cats showed no such inhibition of state 3 respiration and no differences in function from normo- and hyperglycemic control animals except for trends toward loose coupling. Significantly higher brain tissue glucose concentrations were present in hyperglycemic controls as the only metabolite difference compared to normoglycemic controls. At the end of anoxia, hyperglycemic cats exhibited significantly higher cortical lactate and glucose levels but similarly reduced high-energy phosphate concentrations compared to normoglycemic cats. These results demonstrate that increased availability of glucose to gray matter as a consequence of hyperglycemia maintains normal mitochondrial state 3 respiration during exposure to anoxia. Previous survival studies have shown that lower serum glucose concentrations during anoxia are relatively brain protective. This result indicates that the presently described alterations in mitochondrial respiration must be fully reversible.

Long-term effects of nifedipine on carbohydrate and lipid metabolism in hypertensive hemodialyzed patients.

To evaluate long-term effects of nifedipine on carbohydrate and lipid metabolism, 15 hypertensive patients undergoing regular hemodialysis treatment were investigated before nifedipine therapy, after 3 and 9 weeks, and 2 weeks after stopping nifedipine therapy. Three weeks following the administration of nifedipine, both glucose and insulin concentrations decreased significantly from 102.1 +/- 2.6 to 94.9 +/- 2.2 mg/dl and from 19.9 +/- 2.9 to 13.9 +/- 1.7 microU/ml and also remained significantly lower after 9 weeks of nifedipine therapy. This effect was paralleled by a fall of noradrenaline and dopamine. Glucagon levels remained constant. Glucose tolerance tests performed during nifedipine medication and 2 weeks after stopping of nifedipine therapy did not differ significantly. An increase of pyruvate, citric acid cycle intermediates, and ketone bodies--but not of lactate--was registered during nifedipine medication. The observed effects were not completely abolished after the 2-week placebo phase. Our data indicate that nifedipine lowers serum glucose values despite decreased insulin and constant glucagon levels in hypertensive hemodialyzed patients. Considering additionally the behavior of catecholamines and organic acids, the effects could be explained by the improvement of peripheral glucose utilization.

Tolbutamide Increases Hypothalamic Serotonin Activity in the Rat

Sulfonylureas are potent hypoglycemic agents; however, their mechanism of action remains incompletely understood. Recent data indicate that hypothalamic norepinephrine (NE) plays a major role in mediating the central neural regulation of blood glucose. We therefore examined whether the sulfonylurea tolbutamide might lower serum glucose via an effect on hypothalamic NE neuronal activity, and compared the effects with those of 2-deoxyglucose-induced neuroglycopenia and of chronic insulin administration. Serum glucose levels fell and serum insulin levels rose 10, 20, and 30 min after acute tolbutamide injection. Serum glucose concentrations were reduced after chronic tolbutamide administered in drinking water, but serum insulin did not change. Hypothalamic NE neuronal activity was increased 10 min after tolbutamide administration, but not at the later times, nor during chronic tolbutamide administration. However, consistent with a rise in serotonin (5-HT) neuronal activity, hypothalamic 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA/5-HT ratio rose 30 min after acute tolbutamide and during chronic tolbutamide administration. This rise was not due to neuroglycopenia per se, since hypothalamic NE neuronal activity was increased and hypothalamic 5-HT neuronal activity was reduced after 2-deoxyglucose-induced neuroglycopenia. Furthermore, the effect of chronic tolbutamide contrasted with that of chronic insulin administration where hypothalamic NE neuronal activity was increased, while hypothalamic 5-HT neuronal activity was unchanged. We conclude that tolbutamide does not lower serum glucose via a direct effect on hypothalamic NE neuronal activity; however, we note that tolbutamide specifically increases hypothalamic 5-HT neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of carbohydrate-enriched meals on glucose turnover and metabolic clearance rates of glucose in type 2 diabetic patients.

The addition of fructose to natural meals elicits lower serum glucose and immunoreactive insulin responses when compared with that of sucrose and starch meals. Differences in rates of splanchnic glucose appearance and peripheral glucose disposal may be partly responsible. To evaluate the role of both parameters after different carbohydrate-enriched meals, we measured the arterialized venous blood glucose, immunoreactive insulin and gastric inhibitory polypeptide concentrations in seven Type 2 diabetic patients after ingestion of isocaloric test meals. Measurements were made in a random manner on three separate occasions. Fructose, sucrose, and bread supplementation constituted 68% of the total carbohydrate content of each meal. Rates of total glucose appearance, glucose utilization and metabolic clearance rates of glucose were determined by the D3-H-3 glucose prime-continuous infusion technique. The mean fasting glucose levels were similar in the three groups. Mean peak glucose concentrations and integrated incremental areas were significantly lower (p less than 0.02) after the fructose-enriched meals compared with that of either sucrose or bread. The basal arterialized venous blood glucose levels were similar in all three groups. The mean incremental integrated arterialized venous blood glucose area was significantly lower in the fructose group when compared with the sucrose (p less than 0.05) and bread (p less than 0.02) groups. The mean fasting gastric inhibitory polypeptide levels were similar in the three groups. However, the mean incremental integrated gastric inhibitory polypeptide areas were significantly lower in the fructose group compared with the sucrose and bread groups (p less than 0.01 and p less than 0.05 respectively). Basal hepatic glucose outputs were not significantly different in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycosylation abolishes an in vitro insulin-like action of prolactin

Ovine prolactin stimulated 14C-CO2 production from labeled glucose in adipose tissue of hypophysectomized rats in vitro, an insulin-like activity. Glycosylation of the hormone by attachment of a carbohydrate unit at asparagine31 abolished this in vitro insulin-like action. However, neither nonglycosylated nor glycosylated prolactin exhibited in vivo insulin-like action, as they did not lower serum glucose or non-esterified fatty acids in fasted hypophysectomized rats. Hindrance of receptor binding by the carbohydrate unit may account for the absence of in vitro insulin-like activity in glycosylated prolactin, but the dichotomy between in vivo and in vitro insulin-like actions for prolactin remains obscure.