Onset Of Fasting Research Articles

Identifying factors that predict the onset and persistence of fasting for weight control: Prospective findings.

Fasting for weight control is an under-studied behaviour implicated in eating disorders. However, little is known about what factors account for its onset and persistence. This study sought to identify risk and maintenance factors for fasting among 1025 women recruited through an eating disorder self-help platform who completed study measures at baseline and 6month follow-up. Univariate and multivariate logistic regressions were performed to test which variables at baseline predicted the onset (vs. stably asymptomatic) and persistence (vs. remission) of fasting at follow-up. Univariate models showed that higher baseline overvaluation, dissatisfaction, fear of weight gain, generalised and social anxiety, depression, self-esteem deficits and eating disorder symptoms (inflexible eating rules, driven exercise) predicted greater likelihood of fasting onset. Only fear of weight gain and depressive symptoms remained significant in the multivariate model. Higher baseline overvaluation, fear of weight gain, driven exercise, inflexible eating rules, and depression predicted greater likelihood of fasting persistence in univariate models. An adherence to inflexible eating rules and overvaluation remained significant in the multivariate model. Findings shed new light on factors that may account for the development and maintenance of fasting, which have implications for guiding effective interventions targeting this behaviour.

The role of ghrelin in metabolic regulation.

To discuss recent research on the role of ghrelin in the regulation of carbohydrate and lipid metabolism in the context of its wider role in regulating energy balance. Ghrelin possesses a range of centrally and peripherally mediated metabolic actions influencing insulin glucose homeostasis and fatty acid metabolism and appetite. Although acyl ghrelin was previously thought to be the active hormone, recent evidence suggests that des-acyl ghrelin also possesses activity, and the enzyme ghrelin-O-acyl transferase regulates their interconversion. In partnership with insulin and leptin, ghrelin defends against energy deficit by enhancing hunger, conserving carbohydrate and promoting fat oxidation. In the postprandial state, it contributes to satiety, energy storage and favours glucose oxidation. New research suggests a range of new roles including addictive behaviours, cardiovascular protection, neuroprotection and regeneration and perhaps the ageing process. Ghrelin functions primarily as a short-term metabolic switch at the onset of fasting, gearing the fuel economy away from glucose uptake, conserving glucose for vital functions, favouring fatty acid oxidation and triggering food-seeking behaviour. The ghrelin system is a potential target for a range of pharmacological interventions, but its pleiotropic nature makes selective treatments challenging.

Is the British weather anti-Islamic? Prayer times, the ulama and application of the shari’a

In the absence of clear-cut guidance from the primary sources of the shari‘a, how do Muslim scholars derive a workable religious praxis in changing circumstances and which authorities do they invoke in the process? This article explores possible answers to these questions by conducting a detailed analysis of a debate between two groups of Deobandi scholars in Britain over establishing the correct time for the commencement of morning (Fajr) and the onset of fasting for Ramadan. I argue that besides the primary sources, these Deobandi scholars invoke alternate forms of extra-scriptural authority such as the weight of precedence deriving from the akabir (elders) of the Deobandi tradition, as also their reliance on modern scientific knowledge. The article highlights the complex interplay of factors which determines the way that Muslims in Britain negotiate the practice of their religion in new socio-cultural milieu and the way they attempt to incorporate these changes within the parameters of an established religious discourse.

The influence of feeding pattern on changes in plasma ghrelin in the Holstein cow.

ABSTRACTWe measured the plasma ghrelin and cortisol concentrations in non-lactating cows under fixed-time feeding conditions followed by an acute or gradual fasting treatment. During the 4 days before fasting, animals in Group 1 were fed a fixed amount of rations at 0800 and 1600 hr, and those in Group 2 were fed a gradually reduced amount. Thereafter, the plasma ghrelin concentrations of each animal were measured for 40 hr. The plasma ghrelin concentrations, which were low at the onset of fasting, increased before and after 0800 during fasting in Group 1, but not in Group 2. There were no significant differences in the plasma cortisol concentration within or between the groups. It was demonstrated that acute fasting induces elevation of the plasma ghrelin concentration, but that gradual fasting does not. This result suggests that fixed-time and fixed-quantity feeding caused a daily ghrelin rhythm in the cow and that this rhythm influenced changes in plasma ghrelin.

Fasting regulates FSP27 expression in the liver

Fasting regulates FSP27 expression in the liver

Age-related effects of fasting on ketone body production during lipolysis in rats

The age-related effects of fasting on lipolysis, the production of ketone bodies, and plasma insulin levels were studied in male 3-, 8-, and 32-week-old Sprague-Dawley rats. The rats were divided into fasting and control groups. The 3-, 8- and 32-week-old rats tolerated fasting for 2, 5, and 12days, respectively. Fasting markedly reduced the weights of perirenal and periepididymal white adipose tissues in rats in the three age groups. The mean rates of reduction in both these adipose tissue weights during fasting periods were higher in the order of 3>8>32-week-old rats. Fasting transiently increased plasma free fatty acid (FFA), total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups. However, plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the 3-week-old rats reached maximal peak within 2days after the onset of fasting, although these concentrations in the 8- and 32-week-old rats took more than 2days to reach the maximal peak. By contrast, the augmentation of plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups had declined at the end of each experimental period. Thus, the capacity for fat mobilization was associated with tolerance to fasting. Plasma insulin concentrations in the rats in the three age groups were dramatically reduced during fasting periods, although basal levels of insulin were higher in the order of 32>8>3week-old rats. These results suggest that differences in fat metabolism patterns among rats in the three age groups during prolonged fasting were partly reflected the metabolic turnover rates, plasma insulin levels, and amounts of fat storage.

Prophylactic Etoricoxib Is Effective in Preventing “First of Ramadan” Headache: A Placebo‐Controlled Double‐Blind and Randomized Trial of Prophylactic Etoricoxib for Ritual Fasting Headache

Religious fasting is associated with headache. This has been documented as "Yom Kippur headache" and "first of Ramadan headache." Etoricoxib, a Cox-2 inhibitor with a 22-hour half-life, has been shown effective in preventing fasting headache when taken just prior to the 25-hour Yom Kippur fast. We hypothesized that etoricoxib would also be effective in preventing headache during Ramadan, despite the different characteristics of the fast. We performed a double-blind randomized prospective crossover trial of etoricoxib 90mg vs placebo, taken just prior to the onset of fasting, during the first 2 weeks of Ramadan 2010. Healthy adults aged 18-65 years were enrolled. Demographics, headache history and a daily post-fast survey were collected. We compared incidence, time of onset, and intensity of headache on each day and side effects in control and treatment groups. We enrolled 222 patients and 189 completed the post-fast questionnaire (87%). Etoricoxib reduced the incidence of "first of Ramadan" headache by 54% (46% in placebo group [n=92] vs 21% [n=96] in etoricoxib group) (P<.0001, OR 3.19 [95% CI 1.68-6.06]). For days 1-6, the mean number of headache days for the placebo group was 1.60 (n=92) and for the treatment group the mean was 0.86 (n=99) headache days (P=.003). Median severity of headache in the treatment group was significantly lower. In the second week, there was no significant difference in incidence of headache between groups, and the incidence of headache in the placebo group dropped markedly over time. Etoricoxib 90mg taken prior to a 15-hour ritual fast decreases incidence of and attenuates headache during the first 5 days of the month of Ramadan.

Prophylactic Etoricoxib Is Effective in Preventing Yom Kippur Headache: A Placebo‐Controlled Double‐Blind and Randomized Trial of Prophylaxis for Ritual Fasting Headache

Religious fasting is associated with headache. This has been documented as "Yom Kippur Headache" and "First-of-Ramadan Headache." Rofecoxib (Vioxx®), a cyclooxygenase-2 (Cox-2) inhibitor with a 17-hour half-life, has been shown to be effective in preventing fasting headache when taken just prior to the 25-hour Yom Kippur fast. Unfortunately for fasters rofecoxib is no longer available. We hypothesized that etoricoxib, another Cox-2 inhibitor with a longer half-life, would also be effective in preventing fasting headache. We performed a double-blind randomized prospective trial of etoricoxib 120 mg vs placebo, taken just prior to the onset of fasting, Yom Kippur 2008. Healthy adults aged 18-65 years were enrolled from the community. Subjects completed a demographic data form and questions regarding headache history and a post-fast survey on headache during the fast. We compared incidence, time of onset and intensity of headache, general ease of fasting, and side effects in control and treatment groups. We enrolled 211 patients and 195 completed the post-fast questionnaire (92%). Of those subjects receiving etoricoxib (n=99), 36 or 36.4% vs 65 or 67.7% of the placebo group (n=96) developed any headache during the fast (P< .0001). Median severity of headache in the treatment group was significantly lower for the treatment group (3.0 vs 5.0 on a visual analog scale of 10; P= .024). Also, participants in the treatment group reported an easier fast than the placebo group, as compared with previous fasting experience (4.0 vs 3.5 on a scale of 1-5; P< .0001). Etoricoxib 120 mg taken prior to a 25-hour ritual fast decreases incidence of and attenuates fasting headache.

Fasting differentially regulates plasma corticosterone-binding globulin, glucocorticoid receptor, and cell cycle in the gastric mucosa of pups and adult rats

The nutritional status influences gastric growth, and interestingly, whereas cell proliferation is stimulated by fasting in suckling rats, it is inhibited in adult animals. Corticosterone takes part in the mechanisms that govern development, and its effects are regulated in particular by corticosterone-binding globulin (CBG) and glucocorticoid receptor (GR). To investigate whether corticosterone activity responds to fasting and how possible changes might control gastric epithelial cell cycle, we evaluated different parameters during the progression of fasting in 18- and 40-day-old rats. Food restriction induced higher corticosterone plasma concentration at both ages, but only in pups did CBG binding increase after short- and long-term treatments. Fasting also increased gastric GR at transcriptional and protein levels, but the effect was more pronounced in 40-day-old animals. Moreover, in pups, GR was observed in the cytoplasm, whereas, in adults, it accumulated in the nucleus after the onset of fasting. Heat shock protein (HSP) 70 and HSP 90 were differentially regulated and might contribute to the stability of GR and to the high cytoplasmic levels in pups and elevated shuttling in adult rats. As for gastric epithelial cell cycle, whereas cyclin D1 and p21 increased during fasting in pups, in adults, cyclin E slowly decreased, concomitant with higher p27. In summary, we demonstrated that corticosterone function is differentially regulated by fasting in 18- and 40-day-old rats, and such variation might attenuate any possible suppressive effects during postnatal development. We suggest that this mechanism could ultimately increase cell proliferation and allow regular gastric growth during adverse nutritional conditions.

Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4α and PGC1α

Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

Prophylactic COX 2 Inhibitor: An End to the Yom Kippur Headache

Religious fasting is associated with headache. This has been documented as "Yom Kippur Headache" and "First of Ramadan Headache." The Cox2 inhibitor, rofecoxib, has been reported effective in preventing perimenstrual migraine and in preventing recurrence of migraine. Given its 17 hour half-life, we undertook this study to see whether 50 mg rofecoxib taken just prior to the 25 hour Yom Kippur fast would be effective in preventing headache. We performed a double-blind randomized prospective trial of rofecoxib 50 mg versus placebo, taken just prior to the onset of fasting, Yom Kippur 2004. Healthy adults aged 18 to 65 were enrolled from the community and from hospital staff. Subjects completed a demographic data form and questions regarding headache history and a post-fast survey on headache during the fast, headache intensity, general ease of fasting, and side effects. We sent out 170 forms of which 105 were completed and returned. Of those subjects receiving rofecoxib (n = 53), 10 or 18.9% versus 34 or 65.4% of the placebo group (n = 52) had headache at some point during the fast (P < .0001). Severity of headache in the treatment group was significantly less for the treatment group (3.45 vs 6.29 on a visual analog scale of 10 (P= .009)). None of those receiving rofecoxib reported a "more difficult than usual fast" whereas the distribution of difficult to easy fast among the placebo group was more even. Rofecoxib 50 mg taken prior to a 25-hour ritual fast prevents and attenuates fasting headache.

Temporal expression of estrogen receptor α in the hypothalamus and medulla oblongata during fasting: a role of noradrenergic neurons

Fasting-induced LH suppression is augmented by estrogen in female rats. We investigated the temporal changes in the number of estrogen receptor alpha (ERalpha)-immunoreactive (ir) cells in various brain regions in ovariectomized rats fasted for 6, 24, 30, and 48 h, commencing at 1300 h. We also determined the anatomical relationship of ERalpha immunoreactivity and dopamine-beta-hydroxylase (DBH) neurons in the A2 region of the nucleus of the solitary tract (NTS) and the paraventricular nucleus (PVN). The number of ERalpha-ir cells significantly increased after 30 h from the onset of fasting in the PVN and NTS compared with the unfasted controls and was sustained until 48 h. In the A2 region of 48-h fasted rats, 46.75% DBH-ir cells expressed ERalpha, and this was significantly higher than in unfasted controls (8.16% DBH-ir cells expressed ERalpha). In the PVN, most ERalpha-ir neurons were juxtaposed with DBH-ir varicosities. These results suggest that ERalpha is expressed in specific brain regions at a defined time from the onset of fasting. In addition, the anatomical relationship of noradrenergic and ERalpha-ir neurons in the A2 region and PVN may suggest a role for estrogen in increasing the activity of noradrenergic neurons in the A2 region and enhancing sensitivity of the PVN to noradrenergic input arising from the lower brainstem and thereby augmenting the suppression of LH secretion during fasting.

Efeito do padrão alimentar sobre a morfologia da parede ruminal de vacas e carneiros

A manipulação nutricional da capacidade de absorção de ácidos graxos voláteis pela parede do rúmen pode ser uma estratégia para controlar acidose em vacas leiteiras. Objetivando induzir variação morfológica da parede do rúmen através da dieta e estabelecer marcadores morfológicos eficientes para epitélio ruminal, dois experimentos foram relizados. No experimento um, sete vacas com cânula ruminal foram alimentadas com concentrado uma ou quatro vezes ao dia por 19 dias seguidos por 72 horas de jejum. Papilas ruminais foram coletadas nos dias zero, quatro, 12 e 19 do período de tratamento e 24, 48 e 72 horas após o início do período de jejum. Baixa freqüência de alimentação concentrada foi associada a um aumento de insulina plasmática através do tempo (P=0,02) e a um maior (P=0,03) índice mitótico (IM), mas não afetou outros parâmetros morfológicos. No experimento dois, foram realizados dois ensaios não-simultâneos com três ovinos canulados no rúmen, os quais foram submetidos abruptamente a 72 horas de jejum. Papilas ruminais foram coletadas no final do período de alimentação e no final do jejum. O IM foi mais alto no período de alimentação do que no período de jejum (P&lt;0,01), mas outros parâmetros morfológicos não foram capazes de responder à variação nutricional. Entres os marcadores morfológicos estudados o IM parece ser a melhor variável para avaliação da resposta morfológica do epitélio ao plano alimentar. A freqüência de alimentação concentrada pode ser usada para regular a morfologia das papilas ruminais.

Effect of Fasting on c-Fos Expression in the Hypothalamic Nuclei and Nucleus of the Solitary Tract in Male Rats: Time Course Study and the Role of Testosterone.

We have shown that 48-h fasting suppresses luteinizing hormone (LH) secretion in female rats which is enhanced by an estrogenic milieu and mediated by noradrenergic neurons. A similar fasting protocol yielded a suppression of LH secretion in male rats in a testosterone-dependent manner. In this experiment, we intended to identify specific nuclei in the hypothalamus and caudal brainstem that are activated during fasting for 6, 24, 30 or 48 h in castrated male rats with or without chronic testosterone treatment. Fasting started at 1300 h (lights-off at 1900 h). In testosterone-treated castrates, Fos-like-immunoreactive (FL-ir) cells were significantly increased in the paraventricular nucleus, A2 region of the nucleus of the solitary tract, supraoptic nucleus and amygdala 6 h after the onset of fasting but not 24, 30 or 48 h after the onset. On the other hand, FL-ir cells were not significantly different in those areas among fasted castrates compared with unfasted controls. In the A2 region of testosterone-treated castrates, tyrosine hydroxylase- and dopamine-β-hydroxylase-immunoreactive (TH-ir, DBH-ir) cells did not exhibit Fos-like immunoreactivity (FLI). Our results suggest that the absence of food may activate neurons in discrete hypothalamic and brainstem nuclei in male rats at the beginning of fasting and this activation requires an androgenic milieu. The absence of FLI in TH- or DBH-ir cells in the A2 region would indicate that transmitter systems other than catecholaminergic neurons may be involved during the very early stage of 48-h fasting-induced suppression of LH secretion.

Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association.

This statement examines the cardiovascular complications of diabetes mellitus and considers opportunities for their prevention. These complications include coronary heart disease (CHD), stroke, peripheral arterial disease, nephropathy, retinopathy, and possibly neuropathy and cardiomyopathy. Because of the aging of the population and an increasing prevalence of obesity and sedentary life habits in the United States, the prevalence of diabetes is increasing. Thus, diabetes must take its place alongside the other major risk factors as important causes of cardiovascular disease (CVD). In fact, from the point of view of cardiovascular medicine, it may be appropriate to say, “diabetes is a cardiovascular disease.” The most prevalent form of diabetes mellitus is type 2 diabetes. This disorder typically makes its appearance later in life. The underlying metabolic causes of type 2 diabetes are the combination of impairment in insulin-mediated glucose disposal (insulin resistance) and defective secretion of insulin by pancreatic β-cells. Insulin resistance develops from obesity and physical inactivity, acting on a substrate of genetic susceptibility.1 2 Insulin secretion declines with advancing age,3 4 and this decline may be accelerated by genetic factors.5 6 Insulin resistance typically precedes the onset of type 2 diabetes and is commonly accompanied by other cardiovascular risk factors: dyslipidemia, hypertension, and prothrombotic factors.7 8 The common clustering of these risk factors in a single individual has been called the metabolic syndrome. Many patients with the metabolic syndrome manifest impaired fasting glucose (IFG)9 even when they do not have overt diabetes mellitus.10 The metabolic syndrome commonly precedes the development of type 2 diabetes by many years11 ; of great importance, the risk factors that constitute this syndrome contribute independently to CVD risk. Recently, new criteria have been accepted for the diagnosis of diabetes.9 The upper threshold of fasting plasma glucose for the …

Elevated Corticosterone Is Not Required for the Rapid Induction of Neuropeptide Y Gene Expression by an Overnight Fast*

Fasting stimulates corticosterone (B) secretion and the expression and secretion of hypothalamic neuropeptide Y in rats. These studies tested the hypothesis that the rapid and marked fasting-induced increases in plasma B are responsible for stimulation of neuropeptide Y (NPY) gene expression. Plasma leptin and insulin were measured because they are also signals known to affect NPY messenger RNA (mRNA). Intact or adrenalectomized rats given a low fixed level of corticosterone (B replaced) were fasted for 48 h. NPY mRNA in the mediobasal hypothalamus, measured by nuclease protection assay, was elevated similarly above ad lib-fed controls in both intact and B replaced groups at 15 and 48 h after the onset of fasting. NPY immunoreactivity in the mediobasal hypothalamus increased between 3 and 48 h after onset of the fast in intact but not in B replaced groups. The fasting-induced decreases in leptin observed in intact rats at 48 h did not occur in B replaced rats. Fasting-induced decreases in insulin occurred in B replaced rats but not in intact rats. We conclude that: 1) elevated B is not required for fasting-induced increases in hypothalamic NPY gene expression; and 2) decreases in neither leptin nor insulin alone signal the changes that occur in NPY mRNA in fasted rats.

Functional activation of CRH neurons and expression of the genes encoding CRH and its receptors in food-deprived lean (Fa/?) and obese (fa/fa) Zucker rats.

The time course of the action of food deprivation on the functional activation of corticotropin-releasing hormone (CRH) neurons and on the expression of the genes encoding CRH and its receptors of type 1 (CRH1-R) and 2alpha (CRH2-R) in the brain were assessed in lean (Fa/?) and obese (fa/fa) Zucker rats. Fa/? and fa/fa rats were assigned to food deprivation periods of 0, 3, 6, 12, and 24 h. Measurements of Fos immunoreactivity and CRH mRNA were carried out on the same brain sections to assess the state of activation of CRH neurons. In situ hybridization histochemistry was employed to measure the mRNAs encoding CRH and its receptors. In fa/fa rats, food deprivation induced a rapid expression of Fos in CRH cells of several brain regions that include the paraventricular hypothalamic nucleus (PVN), the bed nucleus of the stria terminalis (BNST), the anterodorsal preoptic nucleus, the medial preoptic nucleus, the substantia innominata and Barrington's nucleus. The colocalization of Fos immunoreactivity and CRH mRNA was particularly noticeable in the PVN of fa/fa rats, where the majority of the CRH cells of the parvocellular division of the nucleus displayed Fos-positive nuclei, 12 h after the onset of fasting. In obese rats, food deprivation also produced an increase in the CRH mRNA levels in the BNST as well as high and low expressions of the CRH1-R in, respectively, the PVN and the anterior lobe of the pituitary. The expression of CRH1-R in the PVN of obese rats occurred 12 h after the onset of the deprivation. In Fa/? rats, food deprivation induced no marked activation of the CRH cells, a slow decrease in the CRH mRNA levels in the BNST and the central nucleus of the amygdala, and a gradual decrease in the expression of CRH2-R gene in the ventromedial hypothalamic nucleus. These results demonstrate that food deprivation is capable of generating in obese Zucker rats a stress-like response that translates into a particularly striking activation of the hypothalamic-pituitary-adrenal axis. This response contrasts with that observed in Fa/? rats, in which the action of food deprivation on the CRH system seems more compatible with the known effects of CRH in the regulation of energy balance.

Interrelationships between breeding frequency, timing and outcome in King Penguins Aptenodytes patagonicus: are King Penguins biennial breeders?

King Penguin Aptenodytes patagonicus chick growth is interrupted by a winter fast which extends the length of the breeding cycle (laying to chick independence) to 14–16 months, so that continuous annual successful breeding appears to be impossible. The 3–month laying period imposes further constraints with respect to timing of breeding attempts in relation to the onset of fasting. By the frequent resighting of individually marked birds at Marion Island, we examined the frequency of breeding and the relationships between timing, outcome and frequency in the same and in consecutive years. A total of 3101 adult King Penguins were banded between 1984 and 1991, yielding continuous breeding histories spanning a maximum of 5 years. Most penguins attempted to breed in consecutive years, although the likelihood of taking a year off increased with the number of consecutive attempts. In any one season, about 19% of potentially breeding adults did not breed. Early breeders were more likely to succeed than late breeders and comprised 84% of breeding attempts of known timing. Successful birds in one season usually bred late in the following season, whereas failed attempts were usually followed by an early attempt. Non‐breeding was more likely to occur after a successful outcome than a failed one, and after a year off 93% of birds bred early. It is incorrect to refer to the King Penguin as a biennial breeder.

SEQUENTIAL CHANGES IN SERUM INSULIN CONCENTRATION DURING DEVELOPMENT OF NON-INSULIN-DEPENDENT DIABETES

Changes in serum insulin concentrations during deterioration of glucose tolerance were studied in 81 Pima Indians who worsened from normal to impaired glucose tolerance (IGT); 44 who changed from IGT to non-insulin-dependent diabetes mellitus (NIDDM); 27 who were seen at diagnosis of NIDDM and 1·4-8·5 years later; and 11 subjects who were seen at each of these stages. When their glucose tolerance was normal, subjects who later developed NIDDM had higher fasting and post-load insulin concentrations than controls of similar age and body mass index who did not become diabetic. Onset of IGT or NIDDM was associated with a further increase in fasting insulin concentrations, although a deterioration from IGT to NIDDM was associated with little change in insulin responses to oral glucose in spite of increased blood glucose. After the onset of NIDDM, both fasting and post-load insulin concentrations diminished. These longitudinal data show that, as glucose tolerance worsens, insulin and glucose concentrations in individuals follow the inverted-U-shaped relation previously reported in cross-sectional population studies.

Effect of fasting on glycogen metabolism and activities of glycolytic and gluconeogenic enzymes in the mudskipper Boleophthalmus boddaerti

During starvation, muscle glycogen in Boleophthalmus boddaerti was utilized preferentially over liver glycogen. In the first 10 days of fasting, the ratio of the active‘a’form of glycogen phosphorylase to total phosphorylase present in the liver was small. During this period, the active‘I’form of glycogen synthetase increased in the same tissue. In the muscle, the phosphorylase‘a’activity declined during the first 7 days and increased thereafter while the total glycogen synthetase activity showed a drastic decline during the first 13 days of fasting.The glycogen level in the liver and muscle of mudskippers starved for 21 days increased after refeeding. After 6 and 12 h refeeding, liver glycogen level was 8·5 ± 2·3 and 6·9 ± 4·5 mg·g wet wt 1, respectively, as compared to 5·8 ± l·6mg·g wet wt 1 in unfed fish. Muscle glycogen level after 6 and 12 h refeeding was 0·96±0·76 and 0·82 ± 0·50 mg·g wet wt 1, respectively, as opposed to 0·21 ± 0·12 mg·g wet wt 1 in the 21‐days fasted fish. At the same time, activities of glycogen phosphorylase in the muscle and liver increased while the active‘I’form of glycogen synthetase showed higher activity in the liver. Since glycogen was resynthesized upon refeeding, this eliminated the possibility that glycogen depletion during starvation was due to stress or physical exhaustion after handling by the investigator.Throughout the experimental starvation period, the body weight of the mudskipper decreased, with a maximum of 12% weight loss after 21 days. Liver lipid reserves were utilized at the onset of fasting but were thereafter resynthesized. Muscle proteins were also metabolized as the fish were visibly thinner. However, no apparent change in protein content expressed as per gram wet weight was detected as the tissue hydration state was maintained constant. The increased degradation of liver and muscle reserves was coupled to an increase in the activities of key gluconeogenic enzymes in the liver (G6Pase, FDPase, PEPCK, MDH and PC). The increase in glucose synthesis was possibly necessary to counteract hypoglycemia brought about by starvation in B. boddaerti.