The Impact of Exercise on Bone Health in Type 2 Diabetes Mellitus-a Systematic Review.

PURPOSE OF REVIEW: Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Weight loss in T2DM management may result in lowering of bone mass. In this systematic literature review, we aimed to investigate how exercise affects bone health in people with T2DM. Furthermore, we examined the types of exercise with the potential to prevent and treat bone fragility in people with T2DM. RECENT FINDINGS: Exercise differs in type, mechanical load, and intensity, as does the osteogenic response to exercise. Aerobic exercise improves metabolic health in people with T2DM. However, the weight-bearing component of exercise is essential to bone health. Weight loss interventions in T2DM induce a loss of bone mass that may be attenuated if accompanied by resistance or weight-bearing exercise. Combination of weight-bearing aerobic and resistance exercise seems to be preventive against excessive bone loss in people with T2DM. However, evidence is sparse and clinical trials investigating the effects of exercise on bone health in people with T2DM are warranted.

Glucose-Lowering Drugs and Fracture Risk-a Systematic Review.

PURPOSE OF REVIEW: Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic review was to examine the effects of different classes of glucose-lowering drugs on fracture risk in patients with type 2 DM. The heterogeneity of the included studies did not allow formal statistical analyses. RECENT FINDINGS: Sixty studies were included in the review. Metformin, dipeptidylpeptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter 2-inhibitors do not appear to increase fracture risk. Results for insulin and sulphonylureas were more disparate, although there may be an increased fracture risk related to hypoglycemia and falls with these treatments. Glitazones were consistently associated with increased fracture risk in women, although the evidence was sparser in men. New glucose-lowering drugs are continuously being developed and better understanding of these is leading to changes in prescription patterns. Our findings warrant continued research on the effects of glucose-lowering drugs on fracture risk, elucidating the class-specific effects of these drugs.

Dietary medium-chain saturated fatty acids induce gene expression of energy metabolism-related pathways in adipose tissue of abdominally obese subjects.

BACKGROUND: Dietary medium-chain saturated fatty acids (MC-SFAs) have been shown to reduce total body fat. Previously, we showed that MC-SFAs prevent body fat accumulation, despite weight gain. Here, we aim to explore potential molecular mechanisms underlying the protective effect of MC-SFAs on body fat gain. METHODS: The DairyHealth study examined the long-term effects of milk protein and milk fat with a low or high content of MC-SFA. In this 12 week, randomized, double-blind, diet intervention study, participants consumed 60 g milk protein (whey or casein) and 63 g milk fat (high MC-SFA or low MC-SFA) daily in a two by two factorial design. We used microarrays to measure whole genome gene expression changes in subcutaneous adipose tissue in a subpopulation of 12 participants, 6 in the low MC-SFA+casein group and 6 in the high MC-SFA+casein group. Gene expression of several genes that were found to be changed by MC-SFAs was confirmed in the full study population using qPCR. RESULTS: High MC-SFA resulted in an upregulation of gene expression related to citric acid cycle and oxidative phosphorylation, and a downregulation of gene expression related to complement system and inflammation. CONCLUSIONS: We hypothesize that the beneficial effects of MC-SFAs on prevention of fat accumulation are mediated via increased gene expression related to energy metabolism in the adipose tissue. Decreases in inflammation-related gene expression may have beneficial effects in relation to cardiometabolic diseases.

Milking time and risk of over-milking can be decreased with early teat cup removal based on udder quarter milk flow without loss in milk yield.

Increasing the milk flow rate at which milking is terminated can shorten milking time and increase milking efficiency. The effects on milk yield and composition have not been fully investigated when the take-off is set at the udder quarter level and independent of feeding during milking. The objective of this study was to investigate the effect of 3 take-off levels at the udder quarter level (0.06, 0.3, and 0.48 kg/min) applied with or without feeding during milking on milking time, milk yield, the degree of udder emptying, milk composition, and free fatty acids. In this study, 30 cows were allocated into 6 groups, balanced by lactation number, lactation stage, and milk yield, and subjected to a 3 × 2 factorial arrangement of treatments using a Latin square design. Treatments were applied for 1 wk each. This study demonstrated milking time could be reduced by applying up to a take-off level of 0.48 kg/min on udder quarter level without losing milk yield or compromising milk composition or udder health.

[Leadership behaviour and health - current research state]. / Führungsverhalten und Gesundheit - Zum Stand der Forschung.

The link between leaders' behaviour and health has only recently been the focus of scientific research and the results which already exist on this topic have, to date, not been systematically evaluated or summarized. The objective of this article is to make an attempt to provide a summarised overview of the current state of research. Subject-related databases list 42 publications dealing with the relationship between leaders' behaviour and the state of health and well-being of their employees. The literature discusses leaders' behaviour as being both a stressor (source of stress) and a resource. The publications discussed here also provide the first empirical evidence on the influence of various leadership styles on the health of the employees. In particular, transformational and employee-orientated leadership are considered to be beneficial to health. But the question of how leaders' behaviour influences health has not been satisfactorily explained. In most of the publications included, a direct link was assumed and, in the majority of cases, confirmed empirically. In addition, it also appears that there may be an indirect influence which may be moderated or mediated by, e. g., working conditions or the personality of the individual. The relatively small number of research examinations into the influence of leaders' behaviour on the health and well-being of their staff shows that there is a need for additional research.

Alcohol and type 2 diabetes. A review.

AIMS: To describe a) the association between alcohol consumption and the risk of type 2 diabetes (T2D) and b) the impact of alcohol on the glycemic control with and without anti-diabetic drugs. DATA SYNTHESIS: We searched MEDLINE and the Cochrane Library data base with the key words "Diabetes Mellitus, type 2" and "Alcohol Drinking" in English-language studies in adults. For the first part of the review we selected meta-analyses, review articles and observational studies more recent than year 1990 including at least 1000 participants. For the second part of the review we included all articles more recent than year 1990. Most observational studies find a J-shaped association between alcohol intake and incidence of T2D. Interestingly, drinking pattern plays a role, i.e. binge drinking increases the risk of T2D. Opposing information exists about the influence of beverage type. In T2D the acute effects on plasma glucose, insulin, fatty acids and triglyceride vary, in part depending on concomitant intake of food. Acute alcohol intake does not induce hypoglycemia in diet treated T2D, but increases the risk of hypoglycemia in sulphonylurea treated patients. In most studies, long-term alcohol use is associated with improved glycemic control in T2D. CONCLUSIONS: Alcohol consumption reduces the incidence of T2D, however, binge drinking seems to increase the incidence. Acute intake of alcohol does not increase risk of hypoglycemia in diet treated subjects with T2D, only when sulphonylurea is co-administered. Long-term alcohol use seems to be associated with improved glycemic control in T2D probably due to improved insulin sensitivity.

[Workplace health promotion through human resources development part I: development and evaluation of qualification programme for prevention of psychic stresses]. / Betriebliche Gesundheitsförderung durch Personalentwicklung Teil I: Entwicklung und Evaluation eines Qualifizierungsprogramms zur Prävention psychischer Belastungen.

Caregivers of the residents in nursing homes are exposed to a high degree of physical and mental stress. The first part of this article deals with the development and evaluation of an intervention programme aiming at the staff's qualification to deal with these stresses. The main purpose of the programme was the improvement of the caregiver's methodical, social and self-care competences. A controlled study design was applied to evaluate the training effects. Seventeen homes for the elderly and nursing homes were involved in the pilot study. All participants of the intervention group (eleven homes) assessed their competences, their job conditions and their mental health status at the beginning and at the end of the training. The participants of the control group (six homes) assessed these aspects at the same time, but had no training in between. Furthermore, the intervention group took part in a third survey about twelve weeks after the intervention had been finished. Among the training participants, particularly the self-care skills improved (p=0.01). In addition, occupational stress could be reduced (p=0.01) and the climate with the residents enhanced (p=0.06). Compared to the changes also observed in the control group, statistically significant effects only confined to the change of the climate with the residents (p=0.01). In sum, the evaluation confirms the programme's success to develop the caregiver's professional competences in order to reduce their job stress. Further follow-up-studies are needed to investigate the long-term influence of behavioural prevention programmes like this on employee's health.

[Workplace health promotion through human resources development part II: practical transfer of qualification programme for prevention of psychic stresses]. / Betriebliche Gesundheitsförderung durch Personalentwicklung Teil II: Praxistransfer eines Qualifizierungsprogramms zur Prävention psychischer Belastungen.

This article is a follow-on from the first article on the development and evaluation of an intervention programme aiming to teach the staff of care facilities how to better deal with the mental strain they are exposed to. After a brief review of the programme's goal of 'increasing in-house health through staff development' and of the pilot study, this report initially shows how the findings from the pilot phase have been integrated into the original programme and what modifications have been carried out. For example, elements that proved to be successful such as the setting up of a 'steering circle' have been kept and, in addition, solutions for acknowledged weak points such as the insufficient transfer of the acquired knowledge to everyday work situations have been developed. In order to adequately support health care facilities during the implementation of the programme, additional courses to train multipliers who are to offer the necessary assistance, were carried out. The article also covers the evaluation of the quality of the development programme and of the accompanying implementation of the programme by the multipliers. At the end, a practical example is used to illustrate the issue and to demonstrate what actual shape the implementation at the different facilities can take.

Abnormal postprandial PYY response in insulin sensitive nondiabetic subjects with a strong family history of type 2 diabetes.

OBJECTIVE: Gut-derived hormone peptide YY (PYY) is low in subjects with obesity and type 2 diabetes (T2D). However, it is unknown whether this is a primary defect or a consequence of metabolic disturbances. In this study, we aimed to assess whether low fasting and postprandial PYY secretion is an early defect, potentially promoting the development of obesity and T2D, and whether it is modified by macronutrient content. DESIGN: Prospective cross-sectional cohort study. SUBJECTS: Nine individuals with a strong family history of T2D (REL) and seven age and adiposity matched individuals with no family history of T2D (CON). INTERVENTIONS: Metabolic studies including hyperinsulinemic-euglycemic clamp, dual X-ray absorptiometry and two meal tests containing 1000 kcal with an either high fat (76%) or high carbohydrate (76%) content. MAIN OUTCOME MEASURES: Fasting and postprandial PYY levels were measured and analyzed for potential correlations with markers for adiposity and insulin resistance. RESULTS: Insulin sensitivity was not different between REL and CON. Fasting glucose, insulin, triglycerides and PYY were also not different between groups. However, the postprandial incremental area under curve (AUC) of PYY was significantly lower in REL after the high carbohydrate (HCHO) meal (+27.3 vs +60.6% increase from baseline, P=0.038). The AUC of insulin during HCHO meal correlated negatively with both AUC and fasting level of PYY (r=-0.58 and -0.60, respectively, P<0.05). CONCLUSIONS: A blunted postprandial PYY secretion is observed in a very early stage in the development of T2D in genetically susceptible individuals. This defect precedes the presence of insulin resistance and adiposity, and could therefore predispose to the development of T2D.

The effects of proteins and medium-chain fatty acids from milk on body composition, insulin sensitivity and blood pressure in abdominally obese adults.

BACKGROUND/OBJECTIVES: To investigate whether intake of whey protein and butter naturally enriched in medium-chain fatty acids (MC-SFAs) (C6-C12) affected body composition, insulin sensitivity, blood pressure (BP) and plasma cholesterol concentrations. SUBJECTS/METHODS: A 12-week randomised, double-blinded, intervention study was completed in 52 abdominally obese adults. Subjects were assigned to one of four dietary supplementations: 63 g per day of milk fat with either high- (8.5 g per day) or low-MC-SFA (6.9 g per day) content combined with 60 g per day of whey or casein.We examined changes in the body composition by dual-energy X-ray absorption scan, insulin sensitivity using homoeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda index, and diurnal BP and plasma cholesterol concentrations. Two-factor analysis of variance was used to examine the impact of MC-SFA content and protein type. RESULTS: We observed that lean body mass increased by 981 g (95% confidence interval (CI): 248-1713; P=0.010) after high-MC-SFA compared with low-MC-SFA supplementation. Concomitantly, total body-fat percentage increased by 0.70 percentage points (95% CI: 0.10-1.31; P=0.024) after intake of low-MC-SFA butter compared with intake of high-MC-SFA butter. Both changes were independent of protein type (P=0.96 and P=0.99, respectively). We found no difference in HOMA-IR, Matsuda index, diurnal BP or plasma cholesterol concentrations related to MC-SFA content or protein type. CONCLUSIONS: Enhanced intake of MC-SFA increased the lean body mass and caused a significantly lower total body-fat percentage compared with lower intake of MC-SFA. Consequently, the composition of dairy fat should be considered when evaluating the impact of dairy products on body composition.

Day-to-day variation of blood glucose and insulin responses in NIDDM subjects after starch-rich meal.

OBJECTIVE: To study day-to-day variation of postprandial blood glucose and insulin increments in non-insulin-dependent diabetes mellitus (NIDDM) subjects and to analyze intra- and interperson variance of response. RESEARCH DESIGN AND METHODS: Ten NIDDM subjects attending the outpatient clinic at Aarhus Kommunehospital were studied. The subjects ate three meals of 90 g of white bread, with 7 days between tests. RESULTS: Mean +/- SD areas under the blood glucose response curve (above basal) over a 3-h period were 557 +/- 60, 569 +/- 74, and 565 +/- 67 mM x 180 min (NS), and areas under the insulin-response curve were 3350 +/- 448, 2815 +/- 359 and 3551 +/- 679 mU/L x 180 min (NS) on each of the three occasions. The 95% confidence intervals of blood glucose and insulin areas for the test meal repeated three times were 564 +/- 120 mM x 180 min and 3240 +/- 1645 mU/L x 180 min, respectively. Intra- and interperson components of variance were 25 vs. 75% (glucose) and 78 vs. 22% (insulin) of the total variance. The intraperson components of variance included all sources of variation other than between-person variation. There was no significant correlation between blood glucose and insulin response areas. CONCLUSIONS: A valid estimate of the glycemic response in a single patient is obtained after a single meal. Because of the large between-person variation, paired data should preferably be used when comparing glycemic responses to different foods.

Paradoxical reduction of atherosclerosis in apoE-deficient mice with obesity-related type 2 diabetes.

OBJECTIVE: The effect of obesity and insulin resistance on the development of atherosclerosis was evaluated in apoE-deficient (ApoE(-/-)) mice. A previously described obesity model, in which the hypothalamic satiety center can be destroyed by a single gold thioglucose (GTG) injection, was used. To evaluate the effect of starvation on atherosclerosis ApoE(-/-) mice were food-restricted with 25% less chow than ad libitum-fed control mice. METHODS: Sixty-eight ApoE(-/-) mice were allocated into a control group (n=20), a GTG-injected group (n=28), and a food-restricted group (n=20). The control and food-restricted mice were injected with saline instead of GTG. The control and GTG-injected mice had free access to food, and all mice had free access to water during the study period. RESULTS: After 4 months, the GTG-injected mice were significantly overweight (mean body weight (g): 33 +/- 2.11 vs. 23 +/- 0.24 and 17 +/- 0.31 in control and food-restricted mice, respectively), obese, hypertriglyceridemic, insulin-resistant, hyperinsulinemic (mean plasma insulin (ng/ml): 2.45 and 0.43 in obese and control mice, respectively), and hyperglycemic (mean plasma glucose (mmol/l): 11.03 and 7.80 in obese and control mice, respectively). Unexpectedly, these obese and diabetic mice developed significantly less atherosclerosis compared with lean non-diabetic control mice. Food-restricted mice also developed less atherosclerosis compared to control mice. CONCLUSIONS: These findings may question the usefulness of mouse models in studying the relation of obesity-related type 2 diabetes to atherosclerosis and also the relevance of results obtained in apoE(-/-) mice with reduced weight gain during intervention.

Identification of important mechanical and acoustic parameters for the sensory quality of cocoa butter alternatives.

In this study, the correlation between sensory attributes and the mechanical and acoustic properties of cocoa butter alternatives was elucidated. Needle penetration, cone penetration and compression tests were used to characterise mechanical properties and acoustic properties were evaluated by simultaneous texture and sound analyses. Results were correlated with a descriptive sensory evaluation. A significant correlation was found between hardness (needle penetration) and sensory hardness evaluated upon biting (r=0.91, p<0.05) and between Hencky strain (compression test) and the sensory toughness (r=0.94, p<0.05). In contrast, no significant correlation was found between brittleness (cone penetration) and the sensory brittleness. The use of different mechanical methods shed light on a complex rheological behaviour of fat which demonstrates the importance of not simply relying on results from penetration tests when evaluating fat texture. For instance, a hard fat was perceived very differently depending on the degree of elasticity. A significant correlation was found between sound pressure level (simultaneous sound and texture analyses) and the sensory evaluation of the sound intensity upon breakage (r=0.96 and 0.97, p<0.05). Both hardness and elasticity were found to be of great importance for the intensity of the sound emission i.e. a hard texture with a low degree of flexibility (less elastic) is more likely to provide a rapid energy release upon breakage and thus a high intensity sound emission.

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.

Water volume and consumption time: influence on the glycemic and insulinemic responses in non-insulin-dependent diabetic subjects.

The present study was carried out to see if either the volume of water or the duration of ingestion time influence the postprandial blood glucose and insulin responses in non-insulin-dependent diabetic (NIDDM) subjects. Small test meals containing 40 g carbohydrate as rye bread (100 g) with butter (10 g) and tomatoes (75 g) were given to 10 NIDDM subjects. The meals were taken in random order with either 90 or 600 mL tap water. The meal with 90 mL tap water was ingested over 10 and 30 min. The glycemic responses to isocaloric meals of large and small volumes were similar (338 +/- 56 vs 384 +/- 67 mmol/L.240 min) as were the insulinemic responses (29,424 +/- 6512 min vs 27,140 +/- 6548 mumol/L.240 min). An extension of eating time from 10 to 30 min did not alter the glycemic (384 +/- 67 vs 370 +/- 54 mmol/L.240 min) or the insulinemic response (27,140 +/- 6548 vs 35,670 +/- 10,245 mumol/L.240 min) in the NIDDM patients.

Blood glucose and insulin responses to different meals in non-insulin-dependent diabetic subjects of both sexes.

The influence of sex on glucose and insulin responses in patients with non-insulin-dependent diabetes was studied in 12 men and 11 matched women. Two meals of either 100 g white bread or 60 g (raw weight) white rice were given. Blood glucose response areas to white bread (517 vs 509 mmol/L) and to rice (306 vs 353 mmol/L) over a 300-min observation period were similar in females and males, respectively. Insulin responses showed an identical pattern to that of glucose in females and males--35784 vs 28230 pmol/L after white bread and 28044 vs 19464 pmol/L min after rice (NS) over a 300-min observation period, respectively. Within the two study groups, blood glucose-response areas to white bread were significantly higher than those to rice (P less than 0.05), whereas there were no differences in insulin-response areas within or between the two groups. The glycemic index of rice for females (62 +/- 9; mean +/- SE) and males (66 +/- 5) was similar.

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.

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.

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.