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.

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.

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.

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.

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.

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.

Acute effects of monounsaturated fat on postprandial lipemia and gene expression in first-degree relatives of subjects with type 2 diabetes.

BACKGROUND/OBJECTIVES: Subjects with type 2 diabetes (T2D) and their nondiabetic first-degree relatives (REL) have increased risk of cardiovascular disease (CVD). Postprandial triglyceridemia (PPL), influenced by diet, is an independent risk factor for CVD. Dietary fat elicits increased PPL in T2D compared with nondiabetic controls, but our knowledge of PPL responses to fat in REL is sparse. Our aim was to test the hypothesis that REL respond to a monounsaturated fatty acid (MUFA) challenge with a higher PPL response compared with controls who have no family history of T2D (CON) and that MUFAs exert a differential impact on incretin responses and on the expression of genes involved in carbohydrate and lipid metabolism in muscle and adipose tissues of REL and CON. SUBJECTS/METHODS: A total of 17 REL and 17 CON consumed a meal with 72 energy percent derived from MUFAs (macadamia nut oil). Plasma triglycerides, free fatty acids, insulin, glucose, glucagon-like peptide 1, glucose-dependent insulintropic peptide and ghrelin were measured at baseline and regular intervals until 4 h postprandially. Muscle and adipose tissue biopsies were collected at baseline and at 210 min after the meal. RESULTS: The MUFA-rich meal did not elicit different responses (P>0.05) in PPL, insulin, glucose, incretins or ghrelin in REL and CON. Several genes were differentially regulated in muscle and adipose tissues of REL and CON. CONCLUSIONS: A MUFA-rich meal elicits similar PPL, insulin and incretin responses in REL and CON. MUFAs have a differential impact on gene expression in muscle and adipose tissues in a pattern pointing toward early defects in lipid metabolism in REL.

Effects of concentrated arabinoxylan and ß-glucan compared with refined wheat and whole grain rye on glucose and appetite in subjects with the metabolic syndrome: a randomized study.

BACKGROUND/OBJECTIVES: Several studies emphasise that arabinoxylan and ß-glucan have more beneficial effects on glucose metabolism than low-dietary fibre (DF) meals. Less attention has been paid to the effects of concentrated DF compared with whole grain. We compared the effects of DF and whole grain on glucose, hormone responses and appetite in subjects with the metabolic syndrome (MetS). SUBJECTS/METHODS: Fifteen subjects with MetS participated in this acute, randomised, cross-over intervention study. The test breads provided 50 g of digestible carbohydrate: wheat bread with concentrated arabinoxylan (AX) or ß-glucan (BG), rye bread with kernels (RK) and wheat bread (WB) as control. Blood samples were drawn for 270 min to determine glucose, insulin, glucagon-like peptide-1, glucose-dependent insulinotropic peptide (GIP) and ghrelin. Appetite score was addressed every 30 min. Ad libitum energy intake (EI) was measured 270 min after test meals. RESULTS: Compared with WB, BG and RK induced lower initial glycaemic responses (P<0.001), whereas AX only reduced the glucose peak value (P<0.001). RK reduced insulin (P<0.001) and GIP responses (P<0.001) compared with the other breads. BG lowered insulin responses more than AX (P<0.001). AX, BG and RK increased satiety feeling (P<0.001) more than WB, but did not differ significantly in terms of subsequent EI (P=0.089). CONCLUSION: BG and RK had beneficial impact on the glucose response, whereas AX had only effect on the postprandial glucose peak. The impact of the AX bread was influenced by higher protein content. Whether the metabolic effects of the breads are still present to mixed meals remains to be tested.

Inflammatory and oxidative stress responses to high-carbohydrate and high-fat meals in healthy humans.

The postprandial state is hypothesised to be proinflammatory and prooxidative, but the relative contributions of fat versus carbohydrate are unclear. Therefore, we examined inflammation and oxidative stress responses in serum and skeletal muscle before and after 1000 kcal meals, which were high in either fat or carbohydrate in 15 healthy individuals. Serum and muscle expression of IL6 was elevated 3 hours after each meal, independently of macronutrient composition (P < 0.01). Serum IL18 was decreased after high-fat meal only (P < 0.01). Plasma total antioxidative status and muscle Cu/Zn-superoxide dismutase were decreased after high-carbohydrate meal only (P < 0.05). We conclude that a high-carbohydrate meal may evoke a greater postprandial oxidative stress response, whereas both fat and carbohydrate increased IL6. We speculate that the observed increases in postprandial IL6, without increases in any other markers of inflammation, may indicate a normal IL6 response to enhance glucose uptake, similar to its role postexercise.

[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.

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.

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.

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.

Effect of re-feeding after starvation on biomechanical properties in rat small intestine.

Luminal nutrients are essential for maintaining the structural and functional integrity of the gut. Starvation induces pronounced structural and biomechanical remodelling in the rat small intestine. The present work was done to study the recovery process after resumption of food intake. Twenty-five Wistar rats were allocated to five groups. Four groups fasted for 7 days but had free access to water. One of these groups served as fasted controls and was killed at the end of the fast. The other three groups were re-fed for 2, 4 and 7 days before they were euthanised. The fifth group had free access to food during the whole study (fed controls). The intestinal no-load state, zero-stress state and the stress-strain relationship during distension were studied. The intestinal segments were cut transversely into a series of short ring-shaped segments to obtain the no-load state. Each ring was cut in the radial direction to obtain the zero-stress state. The rats regained the lost body weight (22%) by the 7th day of re-feeding. The lost duodenal mass (40%) and jejunal mass (25%) were regained by the 2nd day whereas the lost mass from ileum (18%) was regained by the 4th day. The fasting-induced morphometric changes were normalised by re-feeding on the 2nd day in the duodenum and jejunum, and on the 4th day in the ileum. The longitudinal stress-strain curves shifted to the right after fasting and shifted back within two days following re-feeding (P<0.05). The circumferential stress-strain curves in the fasted or re-fed rats changed in a similar though less pronounced way. Normal values were reached within 4-7 days for the circumferential direction. In conclusion, fasting-induced biomechanical and structural remodelling were normalised by re-feeding in a time- and location-dependent way.

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.