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K Hermansen

Publications and source records attributed to K Hermansen.

At least 19 recordsLinked to original sources
PubMed2003

Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat.

Stevioside, a glycoside present in the leaves of the plant, Stevia rebaudiana Bertoni (SrB), has acute insulinotropic effects in vitro. Its potential antihyperglycemic and blood pressure-lowering effects were examined in a long-term study in the type 2 diabetic Goto-Kakizaki (GK) rat. Rats were fed 0.025 g x kg(-1) x d(-1) of stevioside (purity > 99.6%) for 6 weeks. An intra-arterial catheter was inserted into the rats after 5 weeks, and conscious rats were subjected to arterial glucose tolerance test (2.0 g x kg(-1)) during week 6. Stevioside had an antihyperglycemic effect (incremental area under the glucose response curve [IAUC]): 985 +/- 20 (stevioside) versus 1,575 +/- 21 (control) mmol/L x 180 minutes, (P <.05), it enhanced the first-phase insulin response (IAUC: 343 +/- 33 [stevioside] v 136 +/- 24 [control] microU/mL insulin x 30 minutes, P <.05) and concomitantly suppressed the glucagon levels (total AUC: 2,026 +/- 234 [stevioside] v 3,535 +/- 282 [control] pg/mL x 180 minutes, P <.05). In addition, stevioside caused a pronounced suppression of both the systolic (135 +/- 2 v 153 +/- 5 mm Hg; P <.001) and the diastolic blood pressure (74 +/- 1 v 83 +/- 1 mm Hg; P <.001). Bolus injections of stevioside (0.025 g x kg(-1)) did not induce hypoglycemia. Stevioside augmented the insulin content in the beta-cell line, INS-1. Stevioside may increase the insulin secretion, in part, by induction of genes involved in glycolysis. It may also improve the nutrient-sensing mechanisms, increase cytosolic long-chain fatty acyl-coenzyme A (CoA), and downregulate phosphodiesterase 1 (PDE1) estimated by the microarray gene chip technology. In conclusion, stevioside enjoys a dual positive effect by acting as an antihyperglycemic and a blood pressure-lowering substance; effects that may have therapeutic potential in the treatment of type 2 diabetes and the metabolic syndrome.

Animals↗
PubMed2003

Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Adult↗
PubMed2002

Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: studies in the diabetic Goto-Kakizaki (GK) rats.

Extracts of leaves from the plant Stevia rebaudiana Bertoni have been used in the traditional treatment of diabetes in Paraguay and Brazil. Recently, we demonstrated a direct insulinotropic effect in isolated mouse islets and the clonal beta cell line INS-1 of the glycoside stevioside that is present in large quantity in these leaves. Type 2 diabetes is a chronic metabolic disorder that results from defects in both insulin and glucagon secretion as well as insulin action. In the present study we wanted to unravel if stevioside in vivo exerts an antihyperglycaemic effect in a nonobese animal model of type 2 diabetes. An i.v. glucose tolerance test (IVGT) was carried out with and without stevioside in the type 2 diabetic Goto-Kakizaki (GK) rat, as well as in the normal Wistar rat. Stevioside (0.2 g/kg BW) and D-glucose (2.0 g/kg BW) were administered as i.v. bolus injections in anaesthetized rats. Stevioside significantly suppressed the glucose response to the IVGT in GK rats (incremental area under the curve (IAUC): 648 +/- 50 (stevioside) vs 958 +/- 85 mM x 120 min (control); P < 0.05) and concomitantly increased the insulin response (IAUC: 51116 +/- 10967 (stevioside) vs 21548 +/- 3101 microU x 120 min (control); P < 0.05). Interestingly, the glucagon level was suppressed by stevioside during the IVGT, (total area under the curve (TAUC): 5720 +/- 922 (stevioside) vs 8713 +/- 901 pg/ml x 120 min (control); P < 0.05). In the normal Wistar rat stevioside enhanced insulin levels above basal during the IVGT (IAUC: 79913 +/- 3107 (stevioside) vs 17347 +/- 2882 microU x 120 min (control); P < 0.001), however, without altering the blood glucose response (IAUC: 416 +/- 43 (stevioside) vs 417 +/- 47 mM x 120 min (control)) or the glucagon levels (TAUC: 5493 +/- 527 (stevioside) vs 5033 +/- 264 pg/ml x 120 min (control)). In conclusion, stevioside exerts antihyperglycaemic, insulinotropic, and glucagonostatic actions in the type 2 diabetic GK rat, and may have the potential of becoming a new antidiabetic drug for use in type 2 diabetes.

Animals↗
PubMed2001

Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study.

AIMS/HYPOTHESIS: The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. METHODS: The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid diet (+2%, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E%). Here, insulin sensitivity was 12.5% lower and 8.8% higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet (+4.1%, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (-5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12% (p < 0.001). CONCLUSIONS/INTERPRETATION: A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).

Adult↗
PubMed2001

Effect of a high monounsaturated fatty acid diet on blood pressure and glucose metabolism in women with gestational diabetes mellitus.

OBJECTIVE: The effect of a diet rich in monounsaturated fatty acids (MUFA) on blood pressure, glycemic control, lipids and insulin sensitivity was evaluated in women with gestational diabetes mellitus. DESIGN AND METHODS: A randomized, unpaired diet intervention was performed in 27 women with gestational diabetes mellitus in an outpatient clinic. After randomization the women received either a high-carbohydrate diet (H-CHO) or a high-MUFA diet (H-MUFA) from the 33rd gestational week of pregnancy. Outcome measures were 24 h ambulatory blood pressure, blood lipids, glycemic control and insulin sensitivity estimated by an intravenous glucose tolerance test. RESULTS: The 24 h diastolic blood pressure increased more in the H-CHO group than in the H-MUFA group (P<0.04). CONCLUSIONS: After 5 weeks of treatment with a MUFA-enriched diet, no increase in 24 h diastolic blood pressure and no adverse effects on blood lipids were seen. The favorable effect on the blood pressure by the MUFA diet is a possible non-medication treatment. The H-MUFA diet had no advantage to the H-CHO diet in ameliorating the decline of insulin sensitivity in third term of pregnancy in GDM.

Adult↗
PubMed2001

Alcohol and glucose counterregulation during acute insulin-induced hypoglycemia in type 2 diabetic subjects.

To investigate the influence of alcohol on glucose counterregulation and recovery during acute insulin-induced hypoglycemia in type 2 diabetic subjects, 8 diet-treated type 2 diabetic subjects were examined twice after an overnight fast. A graded hyperinsulinemic (1 mU/kg/min, 60 to 195 minutes) euglycemic/hypoglycemic clamp was performed with concomitant infusion of 3-(3)H-glucose to assess glucose turnover. After a euglycemic baseline period (150 to 180 minutes), 200 mL of water was taken either alone or with alcohol (0.4 g/kg body weight). Hypoglycemia (plasma glucose nadir, 2.8 mmol/L) was subsequently induced, and the recovery period followed after discontinuation of insulin and the variable glucose infusion. On both study days, circulating concentrations of insulin and glucose were comparable. Alcohol intake markedly increased plasma lactate (area under the curve [AUC], recovery period) (244 +/- 30 v 12 +/- 4 mmol/L x 240 minutes; P = .00009) and suppressed plasma nonesterified fatty acids (NEFA) (AUC, recovery period) (95 +/- 13 v 161 +/- 18 mmol/L x 240 minutes; P = .0008). No differences were found in the counterregulatory response of catecholamines, cortisol, and growth hormone (GH). However, alcohol intake decreased peak glucagon significantly (155 +/- 12 v 200 +/- 17 pg/mL; P = .038). In diet-treated, mild type 2 diabetic subjects, alcohol does not modify recovery from insulin-induced hypoglycemia.

Acute Disease↗
PubMed2001

The effect of chronic exposure to fatty acids on gene expression in clonal insulin-producing cells: studies using high density oligonucleotide microarray.

Fatty acids affect insulin secretion of pancreatic beta-cells. Investigating gene expression profiles may help to characterize the underlying mechanism. INS-1 cells were cultured with palmitate (0, 50, and 200 microM) for up to 44 d. Insulin secretion and expressions of 8740 genes were studied. We found that basal insulin secretion increased in cells exposed to palmitate. The response to glucose stimulation declined on d 44 in cells cultured at 200 microM palmitate. In response to 50 and 200 microM palmitate exposure, expression was changed in 11 and 99 genes on d 2 and 134 and in 159 genes on d 44, respectively. Genes involved in fatty acid oxidation were up-regulated, whereas those involved in glycolysis were down-regulated with 200 microM palmitate. A suppression of insulin receptor and insulin receptor substate-2 gene expression was found on d 44 in cells cultured at 200 microM palmitate. In conclusion, chronic exposure to low palmitate alters insulin secretion as well as gene expression. The number of genes that changed expression was palmitate dose and exposure time dependent. Randle's fatty acid-glucose cycle seems to be operative on the gene transcription level. A modification of expression of various genes may contribute to the functional changes.

Cell Line↗
PubMed2001

Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects.

OBJECTIVE: Consumption of soy protein has recently been shown to improve the blood lipid levels in nondiabetic subjects. The purpose of this study was to evaluate if a dietary supplement of soy protein, isoflavones, and cotyledon fiber (Abalon) affects cardiovascular risk markers, blood glucose, and insulin levels in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Twenty type 2 diabetic subjects participated in a crossover trial. They were randomized to double-blind supplementation for 6 weeks with Abalon (soy protein [50 g/day] with high levels of isoflavones [minimum 165 mg/day] and cotyledon fiber [20 g/day]) or placebo (casein [50 g/day] and cellulose [20 g/day]), separated by a 3-week wash-out period. RESULTS: The results are expressed as means +/- SD. The percentage mean treatment difference between Abalon and placebo demonstrated significantly lower mean values after Abalon for LDL cholesterol (10 +/- 15%, P < 0.05), LDL/UHDL ratio (12 +/- 18%, P < 0.05), apolipoprotein (apo) B100 (30 +/- 38%, P < 0.01), triglycerides (22 +/- 10%, P < 0.05), and homocysteine (14 +/- 21%, P < 0.01), whereas the total cholesterol value tended to be less significant but still lower (8 +/- 15%, P < 0.08). No change occurred in HDL cholesterol, apo B100/apo A1 ratio, plasminogen activator inhibitor 1, factor VIIc, von Willebrand factor, fibrinogen, lipoprotein(a), glucose, HbA1c, or 24-h blood pressure. CONCLUSIONS: These results indicate beneficial effects of dietary supplementation with Abalon on cardiovascular risk markers in type 2 diabetic subjects. This improvement is seen even in individuals with near-normal lipid values.

Aged↗
PubMed2001

Comparison of the soluble basal insulin analog insulin detemir with NPH insulin: a randomized open crossover trial in type 1 diabetic subjects on basal-bolus therapy.

OBJECTIVE: Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose-lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia, dose requirements, and safety. RESEARCH DESIGN AND METHODS: This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin. RESULTS: The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P < 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%) (P = 0.049). CONCLUSIONS: Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.

Adolescent↗
PubMed2000

[Proper advice on nutrition. Recommendations concerning the conduct of the nutritional news].

The Committee on Proper Conduct in Public Advice on Nutrition, set up by the Danish Nutrition Council, has produced recommendations to persons involved in communicating results of nutrition research. The guidelines are targeted on scientists, industry, journalists and publishers as well as consumers to facilitate proper conduct in communication of own or other scientists' research results, which might influence consumers' choice and intake of food. The results are presented as recommendations and checklists providing the necessary requirements to bring people in a position to make the best possible evaluation of the new scientific results and to put the results into their proper perspective. The aim of this report is to improve the process so that the communicator focuses on the background information necessary for the reader/listener/viewer in the current situation to achieve a balanced view and benefit from the new scientific result.

Choice Behavior↗
PubMed2000

Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity.

The natural sweetener stevioside, which is found in the plant Stevia rebaudiana Bertoni, has been used for many years in the treatment of diabetes among Indians in Paraguay and Brazil. However, the mechanism for the blood glucose-lowering effect remains unknown. To elucidate the impact of stevioside and its aglucon steviol on insulin release from normal mouse islets and the beta-cell line INS-1 were used. Both stevioside and steviol (1 nmol/L to 1 mmol/L) dose-dependently enhanced insulin secretion from incubated mouse islets in the presence of 16.7 mmol/L glucose (P < .05). The insulinotropic effects of stevioside and steviol were critically dependent on the prevailing glucose concentration, ie, stevioside (1 mmol/L) and steviol (1 micromol/L) only potentiated insulin secretion at or above 8.3 mmol/L glucose (P < .05). Interestingly, the insulinotropic effects of both stevioside and steviol were preserved in the absence of extracellular Ca2+. During perifusion of islets, stevioside (1 mmol/L) and steviol (1 micromol/L) had a long-lasting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). To determine if stevioside and steviol act directly on beta cells, the effects on INS-1 cells were also investigated. Stevioside and steviol both potentiated insulin secretion from INS-1 cells (P < .05). Neither stevioside (1 to 100 micromol/L) nor steviol (10 nmol/L to 10 micromol/L) influenced the plasma membrane K+ adenosine triphosphate ((K+)ATP)-sensitive channel activity, nor did they alter cyclic adenosine monophosphate (cAMP) levels in islets. In conclusion, stevioside and steviol stimulate insulin secretion via a direct action on beta cells. The results indicate that the compounds may have a potential role as antihyperglycemic agents in the treatment of type 2 diabetes mellitus.

ATP-Binding Cassette Transporters↗
PubMed2000

Endothelin-1 (ET-1)-potentiated insulin secretion: involvement of protein kinase C and the ET(A) receptor subtype.

Endothelin-1 (ET-1), a potent vasoconstrictor peptide of endothelial origin, is capable of influencing hormone secretion from endocrine tissues, eg, pancreatic islet cells. We have shown a direct stimulatory effect of ET-1 on insulin secretion from isolated mouse islets of Langerhans. However, it is unknown as to whether the peptide acts through specific receptors on the islet cells and which mechanisms are involved in this insulinotropic action. We have therefore used the specific ET(A) receptor antagonist BQ123, the ET(B) receptor agonist BQ3020, and classic alpha- and beta-adrenergic and cholinergic antagonists. ET-1 (100 nmol/L) stimulated insulin secretion from islets incubated at 8.3, 11.1, 16.7, and 25 mmol/L glucose (P < .05). At 3.3 mmol/L glucose, no alteration in insulin secretion was found. The cholinergic receptor antagonist atropine (5 micromol/L) or the adrenergic receptor antagonists propranolol (5 micromol/L) or phentolamine (5 micromol/L) did not affect ET-1 (100 nmol/L)-stimulated insulin secretion. BQ123 (10 pmol/L to 10 nmol/L) and BQ3020 (1 nmol/L to 1 micromol/L) had no effect on glucose (16.7 mmol/L)-stimulated insulin secretion, but BQ123 counteracted the stimulatory effect of ET-1 (100 nmol/L) at concentrations of 1 nmol/L to 10 micromol/L (P < .01). We also studied the relative role of protein kinase C (PKC) and a Wortmannin-sensitive pathway for ET-1-induced insulin secretion using 12-O-tetradecanoyl phorbol-13-acetate (TPA), Calphostin C, and Wortmannin, respectively. At 5.6 mmol/L glucose, ET-1 (100 nmol/L) had no effect per se, whereas in the presence of 1 micromol/L TPA, which acutely stimulates PKC, the peptide did potentiate insulin secretion (P < .05). Furthermore, the insulinotropic effect of ET-1 at 16.7 mmol/L glucose was counteracted by the PKC inhibitor Calphostin C (P < .05) and by downregulation of PKC by 24 hours of exposure of islets to TPA (0.5 micromol/L, P < .05). Wortmannin (1 micromol/L) did not alter ET-1-potentiated insulin secretion. In conclusion, our results suggest that ET-1 acts through specific ET-1 receptors, most likely the ETA subtype. Furthermore, PKC plays an essential role in the insulinotropic action of ET-1 in mouse islets.

Adrenergic Antagonists↗
PubMed2000

Diet, blood pressure and hypertension.

Prevention of hypertension, and control of blood pressure in patients with hypertension, are necessary for the reduction of cardiovascular morbidity and mortality. Lifestyle modifications are one of the most important tools for effective lowering of blood pressure. Most randomized controlled studies have shown that even a modest weight loss of 3-9% is associated with a significant reduction in systolic and diastolic blood pressure of roughly 3 mm Hg in overweight people. Limitation of sodium chloride in food has historically been considered the critical change for reducing blood pressure. Changes in sodium intake do affect blood pressure in older persons and in patients with hypertension and diabetes, whereas its role in population blood pressure has proven controversial. Recent meta-analyses indicate that adequate intake of minerals, e.g. potassium and probably calcium, rather than restriction of sodium, should be the focus of dietary recommendations. Although epidemiological data point to a direct relation between the intake of saturated fat, starch and alcohol, as well as an inverse relationship to the intake of omega-3 fatty acids and protein, our knowledge about macronutrients and blood pressure is scanty. It may well prove more productive to look at food instead of placing emphasis on single nutrients. Thus the Dietary Approaches to Stop Hypertension (DASH) demonstrates that a diet rich in fruits, vegetables, low-fat dairy products, fibre and minerals (calcium, potassium and magnesium) produces a potent antihypertensive effect. Such a diet is not very restrictive and should not produce compliance problems. Further high-quality research on the influence of macronutrients and food will yield data for updated recommendations, enabling better prevention and control of the blood pressure problem.

Alcohol Drinking↗
PubMed2000

Glycaemic index of parboiled rice depends on the severity of processing: study in type 2 diabetic subjects.

OBJECTIVE: To study the influence of parboiling and the severity of the process on glycaemic and insulinaemic responses to rice in type 2 diabetes. Moreover, to examine changes in starch structure related to parboiling, which may affect the metabolic responses and digestibility. DESIGN: Nine type 2 diabetic subjects ingested four test meals: white bread (WB) and three meals of cooked polished rice of the same variety being non-parboiled (NP), mildly traditionally parboiled (TP) and severely pressure parboiled (PP). The participants ingested the test meals (50 g available carbohydrates) on separate occasions after an overnight fast. SETTING: Outpatient clinic, Dept. Endocrinology and Metabolism, Aarhus University Hospital, Denmark. RESULTS: All three rice samples elicited lower postprandial plasma glucose response (NP: 335+/-43; TP: 274+/-53; PP: 231+/-37 mmol/1*180 min.; means+/-s.e.m.) than white bread (626+/-80; P<0.001), within rice samples PP tended to be lower than NP (P=0.07). The glycaemic indices were: NP: 55+/-5, TP: 46+/-8 and PP: 39+/-6, and lower for PP than NP (P<0.05). The insulin responses were similar for the three rice meals, which were all lower than that to white bread (P<0.001). Differential scanning calorimetry showed the presence of amylose-lipid complexes in all rice samples and of retrograded amylopectin in PP. Amylose retrogradation was not detected in any of the rice samples. CONCLUSIONS: All rice test meals were low-glycaemic in type 2 diabetic subjects. There was no effect of TP on glycaemic index, whereas PP reduced the glycaemic index by almost 30% compared to NP. SPONSORSHIP: The Royal Veterinary and Agricultural University, Aarhus University Hospital, Danish International Development Assistance (DANIDA), Ministry of Foreign Affairs and the 'Konsul Johannes Fogh-Nielsens og Fru Ella Fogh-Nielsens Legat' foundation.

Aged↗
PubMed1999

The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells.

AIMS/HYPOTHESIS: The circulating concentrations of endothelin-1 (ET-1), a peptide derived from endothelium, are increased in hypertension and diabetes. Endothelin-1 has recently been shown to be an insulinotropic agent. The mechanism of action of endothelin-1 on the endocrine pancreas has not yet been clarified. METHODS: We investigated the action of endothelin-1 on the insulin secretion, the binding of (125)I-ET-1 to beta cells as well as its effects on purified beta and non-beta cells from normal rats. The expression of endothelin receptors in alpha- and beta-cell lines and in normal rat islets was also studied. RESULTS: First, we studied the effects of endothelin-1 on insulin secretion from beta-cell lines (INS-1, betaTC3 and MIN6). At all endothelin-1 concentrations applied (1 pmol/l to 1 micromol/l) no change in insulin secretion was found. Ligand-binding experiments on betaTC3 cells showed no specific binding of (125)I-ET-1. A prominent expression of ET(A)-receptor mRNA in an alpha-cell line (alphaTC1.9) and in normal rat islets was found whereas no expression was found in INS-1 cells. No influence of endothelin-1(1 micromol/l) on insulin secretion stimulated by glucose was detected from purified beta cells. Endothelin-1-(100 nmol/l) increased, however, both insulin and glucagon secretion from a mixture of purified beta and non-beta cells indicating that alpha cells seem to have a key role for the action of ET-1 on insulin secretion. CONCLUSION/INTERPRETATION: The insulinotropic impact of endothelin-1 is not caused by a direct action on the beta cells but seems to be mediated by a paracrine action, probably secondary to enhanced release of glucagon from the endothelin receptor positive alpha cells. [Diabetologia (1999) 42: 1302-1307]

Animals↗
PubMed1999

Differential effects of cis and trans fatty acids on insulin release from isolated mouse islets.

In vitro and in vivo studies in animals have shown that elevated levels of free fatty acids (FFAs) induce impaired beta-cell function corresponding to the abnormalities observed in non-insulin-dependent diabetes mellitus (NIDDM). Previously, it was demonstrated that the chain length and degree of unsaturation are of importance for the insulinotropic effect of fatty acids. However, it is not known if the spatial configuration of the fatty acid influences beta-cell function. The present study examines whether cis and trans fatty acids acutely influence insulin release and glucose oxidation in isolated mouse islets in the same way and to the same extent. Thus, we studied the impact of both cis and trans forms of C 18:1 fatty acids. We found that cis and trans vaccenic acid (cis and trans C 18:1 delta11), as well as oleic acid (cis C 18:1 delta9) and elaidic acid (trans 18:1 delta9), caused a dose-dependent increase in glucose (16.7 mmol/L)-stimulated insulin secretion during static islet incubations. The maximal stimulatory effect for cis and trans vaccenic acid and for oleic and elaidic acid was observed at concentrations of 2.0 and 3.0 mmol/L, respectively. The trans isomers, trans vaccenic and elaidic acid, elicited a higher maximal insulin output than the respective cis isomers, cis vaccenic and oleic acid. In the presence of another insulin secretagogue, L-leucine, trans vaccenic but not elaidic acid caused a higher response than their cis isomeric fatty acids. The higher potency of trans fatty acids compared with the cis forms was confirmed in perifusion experiments. Both cis and trans C 18:1 fatty acids stimulated insulin secretion in a glucose-dependent manner. Also, glucose oxidation was influenced differentially by the isomers of fatty acids. Glucose oxidation at 16.7 mmol/L glucose was significantly inhibited by oleic and cis vaccenic acid compared with elaidic and trans vaccenic acid, respectively. In summary, our results demonstrate that the fatty acid spatial configuration modulates glucose oxidation and insulin secretion in mouse beta cells.

Animals↗
PubMed1999

Alcohol and postexercise metabolic responses in type 2 diabetes.

The objective was to investigate the impact of the combination of exercise and alcohol on the metabolic response in nonfasting and fasting type 2 diabetic subjects. In part 1, 12 untrained middle-aged type 2 diabetic subjects participated on 3 test days. On each day, they ingested a light meal (1,824 kJ) containing 48 energy percent (E%) carbohydrate, 38 E% fat, and 14 E% protein. The meal was followed by either (A) rest or (B) 30 minutes of exercise (40% of maximum O2 consumption [VO2max]) or (C) taken with alcohol (0.4 g/kg body weight) followed by 30 minutes of exercise (40% of VO2max). In part 2, 11 untrained middle-aged type 2 diabetic subjects participated on 4 test days without a meal. The subjects were either (A) resting, (B) drinking alcohol (0.4 g/kg body weight), (C) exercising 30 minutes (40% of VO2max), or (D) drinking alcohol (0.4 g/kg body weight) and exercising 30 minutes (40% of VO2max). On each test day, regular blood samples were drawn for 4 hours for analysis of glucose, insulin, lactate, triglycerides, nonesterified fatty acid (NEFA), and ethanol. Comparing exercise and rest following a light meal (part 1, no change (7%) occurred in the plasma glucose response area (642 +/- 119 v 724 +/- 109 mmol x L(-1) x 240 min, NS). However, it was significantly reduced (by 27%) in response to exercise and alcohol (509 +/- 98 v 724 +/- 109 mmol x L(-1) x 240 min; P = .03). Similar serum insulin response areas were obtained. After exercise and alcohol, plasma lactate increased compared with the resting state (2.2 +/- 0.2 v 1.6 +/- 0.1 mmol x L(-1), P = .004) and with exercise alone (2.2 +/- 0.2 v 1.8 +/- 0.2 mmol x L(-1), P = .04). Serum NEFAs were significantly reduced by exercise and alcohol compared with the resting state (0.50 +/- 0.04 v 0.65 +/- 0.06 mmol x L(-1), P = .008) and with exercise alone (0.50 +/- 0.04 v 0.61 +/- 0.05 mmol x L(-1), P = .02). Similar serum triglycerides were found. During the fasting state (part 2), similar plasma glucose response areas were obtained in the four situations. The insulin response area to exercise and alcohol increased significantly compared with the resting state (3,325 +/- 744 v 882 +/- 295 pmol x L(-1) x 240 min, P = .02) and with exercise alone (3,325 +/- 744 v 1,328 +/- 422 pmol x L(-1) x 240 min, P = .007). No difference was found compared with alcohol alone. Plasma lactate was higher after alcohol intake versus the resting state (1.9 +/- 0.1 v 1.3 +/- 0.1 mmol x L(-1), P = .003), as well as after exercise and alcohol (1.9 +/- 0.1 v 1.3 +/- 0.1 mmol x L(-1), P = .01). After exercise and alcohol serum NEFAs were significantly reduced compared with the resting state (0.43 +/- 0.02 v 0.64 +/- 0.02 mmol x L(-1), P < .001), alcohol alone (0.43 +/- 0.02 v 0.51 +/- 0.02 mmol x L(-1), P < .001), and exercise alone (0.43 +/- 0.02 v 0.64 +/- 0.02 mmol x L(-1), P < .001). Serum triglycerides were similar in the four situations. We conclude that moderate exercise with or without moderate alcohol intake does not cause acute hypoglycemia either after a light meal or in the fasting state in untrained overweight type 2 diabetic subjects.

Blood Glucose↗