Insulin sensitivity and liver glucose production in the rat are influenced by lifetime food restriction (original) (raw)
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Blood glucose regulation during fasting in rats under food restriction since birth
Brazilian Archives of Biology and Technology, 2011
The effect of severe food restriction since birth on regulation of fasting glycemia in male Wistar rats was investigated. The control group (CG) had free supply of chow, while the restriction group (RG) received 50% of the amount ingested by the CG. The experiments were done in adult (60 days) overnight fasted rats in which glycemia, liver free glucose levels and hepatic glycogen concentration were measured. In part of the experiments in situ liver perfusion was done. The results showed that livers from the RG had higher glycogenolysis rates but lower gluconeogenesis rates from L-alanine (10 mM). Since RG showed maintained glycemia during fasting, it could be concluded that livers from RG produced glucose preferentially from glycogenolysis in detriment of gluconeogenesis. These findings demonstrated that in spite of severe caloric restriction, the metabolic adaptations of the liver did exist to assure the maintenance of blood glucose for brain supply during fasting.
Dietary Fat and Carbohydrates Differentially Alter Insulin Sensitivity During Caloric Restriction
Gastroenterology, 2009
Reeds, Dominic N.; Finck, Brian N.; Mayurranjan, Mitra S.; Patterson, Bruce W.; and Klein, Samuel, "Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction". Gastroenterology, 136, 5, 1552Gastroenterology, 136, 5, -1560Gastroenterology, 136, 5, . 2009. Paper 21.
Metabolic consequences of food restriction in rats☆
Physiology & Behavior, 1981
Some aspects of carbohydrate metabolism were studied in rats subjected to food restriction (single daily meal offered during two hours, either diurnal or nocturnal) for a week. Nocturnal preference for the nocturnal meal was patent in spite of food restriction, inasmuch as the rats fed from 8:00 to 10:00 p.m. ingested significantly more than those fed from 8:00 to 10:00 a.m. The amount of food ingested by rats of both groups was lower than that ingested by the animals with free access to food (as evaluated in 24 hours); nevertheless, both food-restricted groups did not lose weight for the duration of the experiments. The more prominent carbohydrate metabolic adaptations to food-restriction were: (1) high hepatic glycogen concentration during the intermeai periods; (2) hyperglycemia in the 12, 14 and 16 hour intermeal periods; (3) insulinemia was lower than in rats having free access to food all day long; (4) gastric emptying was delayed. Food restriction Carbohydrate metabolism Feeding behavior COHN et al. [l] and Cohn and Joseph [2] observed that rats ~This research was supported by S~o Paulo State Foundation (FAPESP), National Research Council (CNPq) and FINEP. ~Reprints should be requested from this author.
Insulin Control of Glucose Metabolism in Man
Journal of Clinical Investigation, 1975
During the glucose clamp experiments plasma insulin levels reached a plateau of 95±8 /U/ml. Over the entire range of insulin levels studied, glucose losses were best correlated with levels of insulin in a slowly equilibrating insulin compartment of a three-compartment insulin model. A proportional control by this compartment on glucose utilization was adequate to satisfy the observed data. Insulin also rapidly decreased the endogenous glucose production to 33% of its basal level (0.58 mg/ kg per min), this suppression being maintained for at least 40 min after exogenous insulin infusion was terminated and after plasma insulin concentrations had returned to basal levels. The change in glucose utilization per unit change in insulin in the slowly equilibrating insulin compartment is proposed as a new measure for insulin sensitivity. This defines insulin effects more precisely than previously used measures, such as plasma glucose/plasma insulin concentration ratios. Glucose clamp studies and the modeling of the coupled kinetics of glucose and insulin offers a new and potentially valuable tool to the study of altered states of carbohydrate metabolism.
Effects of insulin-induced hypoglycaemia on energy intake and food choice at a subsequent test meal
Diabetes-metabolism Research and Reviews, 2004
Background and aimsHypoglycaemia is assumed to increase food intake, but there is little data on the magnitude or qualitative nature of this effect. We have therefore investigated the effects of insulin-induced hypoglycaemia on food intake at a test meal.Hypoglycaemia is assumed to increase food intake, but there is little data on the magnitude or qualitative nature of this effect. We have therefore investigated the effects of insulin-induced hypoglycaemia on food intake at a test meal.MethodsSixteen healthy men (age 29.8 ± 11 years; mean ± SD) were studied; either insulin (0.05 units/kg) or saline was given intravenously in a double-blind crossover design. Blood glucose was monitored at regular intervals. Participants were given an ad libitum breakfast 20 min after injections and food intake and appetite scores were recorded.Sixteen healthy men (age 29.8 ± 11 years; mean ± SD) were studied; either insulin (0.05 units/kg) or saline was given intravenously in a double-blind crossover design. Blood glucose was monitored at regular intervals. Participants were given an ad libitum breakfast 20 min after injections and food intake and appetite scores were recorded.ResultsBlood glucose was unchanged following saline (4.3 ± 0.4 to 4.4 ± 0.3 mmol/L). There was a transient decline in blood glucose after insulin with a nadir at 20 min (4.31 ± 0.34 to 2.41 ± 0.45 mmol/L, p < 0.0001), which returned to baseline at 40 min. Total energy intake was 17% higher (1701.1 ± 895.3 kcal vs 1427.7 ± 815 kcal, p = 0.026) following insulin administration compared to that following saline. Macronutrient analysis revealed a significant increase in high-fat foods (muffins) (69.2 ± 54.1 vs 29 ± 42.3 g, p = 0.009) after insulin. Appetite scores were similar after saline and insulin despite these changes in food intake.Blood glucose was unchanged following saline (4.3 ± 0.4 to 4.4 ± 0.3 mmol/L). There was a transient decline in blood glucose after insulin with a nadir at 20 min (4.31 ± 0.34 to 2.41 ± 0.45 mmol/L, p < 0.0001), which returned to baseline at 40 min. Total energy intake was 17% higher (1701.1 ± 895.3 kcal vs 1427.7 ± 815 kcal, p = 0.026) following insulin administration compared to that following saline. Macronutrient analysis revealed a significant increase in high-fat foods (muffins) (69.2 ± 54.1 vs 29 ± 42.3 g, p = 0.009) after insulin. Appetite scores were similar after saline and insulin despite these changes in food intake.ConclusionsTransient insulin-induced hypoglycaemia increases energy intake. Participants consumed more fat after insulin compared to that after saline. High-fat foods can lead to passive overconsumption and have a low glycaemic index, which may prolong hypoglycaemia. Both factors could ultimately promote weight gain in individuals with recurrent hypoglycaemia. Copyright © 2004 John Wiley & Sons, Ltd.Transient insulin-induced hypoglycaemia increases energy intake. Participants consumed more fat after insulin compared to that after saline. High-fat foods can lead to passive overconsumption and have a low glycaemic index, which may prolong hypoglycaemia. Both factors could ultimately promote weight gain in individuals with recurrent hypoglycaemia. Copyright © 2004 John Wiley & Sons, Ltd.
Whole body and hepatic insulin action in normal, starved, and diabetic rats
1991
In normal (N), 3-days starved (S), and streptozotocin-treated (65 mg/kg) 3-days diabetic (D) rats we examined the in vivo doseresponse relationship between plasma insulin levels vs. whole body glucose uptake (BGU) and inhibition of hepatic glucose production (HGP) in conscious rats, as determined with the four-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-"HIglucose infusion. Twelve-hour fasting (basal) HGP was 3.0 t 0.2, 2.1 t 0.2, and 5.4 t 0.5 mg/min in N, S, and D rats, respectively. Next, all rats were clamped at matched glycemia (6 mM). Lowering plasma glucose in D rats from t20 to 6.0 mM did not increase plasma norepinephrine, epinephrine, glucagon, and corticosterone levels. For BGU, insulin sensitivity was increased (70 t 11 pU/ml) in S and unchanged (113 t 21 pU/ml) in D compared with N rats (105 t 10 pU/ml). Insulin responsiveness was unchanged (12.4 t 0.8 mg/min) in S and decreased (8.5 t 0.8 mg/min) in D compared with N rats (12.3 t 0.7 mg/min). For HGP, insulin sensitivity was unchanged (68 t 10 pU/ml) in S and decreased (157 t 21 pU/ml) in D compared with N rats (71 t 5 ,uU/ml). Insulin responsiveness was identical among N, S, and D rats (complete suppression of HGP). In summary, 1) insulin resistance in D rats is caused by hepatic insensitivity and by a reduction in BGU responsiveness. 2) S rats show normal hepatic insulin action, but insulin sensitivity for BGU is increased. Therefore, S and D rats both suffering from a comparable catabolic state (lo-15% body wt loss in 3 days) show opposite effects on in vivo insulin action. This indicates that in vivo insulin resistance in D rats is not caused by the catabolic state per se. MATERIALS AND METHODS Animals and housing. Male Wistar rats (300-350 g) with free access to a complete laboratory rat diet
American Journal of Physiology Regulatory Integrative and Comparative Physiology, 2000
Díaz-Muñ oz, Mauricio, Olivia Vá zquez-Martínez, Raú l Aguilar-Roblero, and Carolina Escobar. Anticipatory changes in liver metabolism and entrainment of insulin, glucagon, and corticosterone in food-restricted rats. Am J Physiol Regulatory Integrative Comp Physiol 279: R2048-R2056, 2000.-Restricted feeding schedules entrain behavioral and physiological circadian rhythms, which depend on a food-entrainable oscillator (FEO). The mechanism of the FEO might depend on digestive and endocrine processes regulating energy balance. The present study characterizes the dynamics of circulating corticosterone, insulin, and glucagon and regulatory parameters of liver metabolism in rats under restricted feeding schedules. With respect to ad libitum controls, food-restricted rats showed 1) an increase in corticosterone and glucagon and a decrease in insulin before food access, indicating a predominant catabolic state; and 2) a reduction in lactate-to-pyruvate and -hydroxybutyrate-toacetoacetate ratios, indicating an oxidized cytoplasmic and mitochondrial redox state in the liver metabolism. All these changes were reversed after feeding. Moreover, liver energy charge in food-restricted rats did not show a significant modification before feeding, despite an increase in adenine nucleotides, but showed an important decrease after food intake. Variations detected in the liver of food-restricted rats are different from those prevailing under 24-h fasting. These observations suggest "anticipatory activity" of the liver metabolism to optimize the processing of nutrients to daily feeding. Data also suggest a possible relationship of the liver and endocrine signals with the FEO.
American Journal of Physiology-Endocrinology and Metabolism, 2000
The availability of the Goto-Kakisaki (GK) rat model of non-insulin-dependent diabetes mellitus prompted us to test the effect of a limited period of undernutrition in previously diabetic young rats on their insulin secretion and insulin action during adult age. Four-week-old female GK rats were either food restricted (35% restriction, 15% protein diet) or protein and energy restricted (35% restriction, 5% protein diet) for 4 wk. Food restriction in the young GK rat lowered weight gain but did not aggravate basal hyperglycemia or glucose intolerance, despite a decrease in basal plasma insulin level. Furthermore, the insulin-mediated glucose uptake by peripheral tissues in the GK rat was clearly improved. We also found that food restriction, when it is coupled to overt protein deficiency in the young GK rat, altered weight gain more severely and slightly decreased basal hyperglycemia but conversely aggravated glucose tolerance. Improvement of basal hyperglycemia was related to repres...
Clinical Nutrition, 2005
Background & Aims: Starvation decreases insulin sensitivity and glucose tolerance in both lean and obese (OB) non-diabetic subjects. Influence of drastic calorie reduction on insulin resistance in patient with type 2 diabetes (T2DM) is not known. Methods: We enrolled 10 T2DM (diabetes duration 11.177.9 years) and 10 OB age and weight-matched subjects and performed isoglycaemic hyperinsulinaemic clamp (two 120 min phases of 60 and 120 mIU min À1 m À2 i.v. insulin) with indirect calorimetry at baseline and after 60 h of fasting. Results: After starvation insulin-mediated glucose disposal decreased significantly in both hyperinsulinaemic phases in T2DM (phase 1: from 46728 to 33717, Po0:04; phase 2 from 122747 to 80730 mg kg À1 min À1 , Po0:01) as well as in OB (phase 1: from 94752 to 52724, Po0:04; phase 2: from 131746 to 106743 mg kg À1 min, Po0:01). Both oxidative and non-oxidative components of glucose disposal tended to be reduced after fasting. A change of insulin sensitivity was found to be highly dependent upon pre-starvation conditions: more insulin resistant subjects tended to maintain (or modestly improve) insulin resistance whilst subjects with better insulin sensitivity tended to worse it. Conclusion: Insulin sensitivity worsens similarly in both T2DM and OB subjects during 60-h fast. The change is probably predictable according to pre-starvation insulin sensitivity.