Oral insulin improves metabolic parameters in high fat diet fed rats

ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL) standard chow group; high fat diet low carbohydrates group (HFD) and HFD plus daily oral 20U insulin gavage (HFD+INS). Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001), fasting glucose and triglycerides serum levels (p<0,05) an increased intestinal weight of distal ileum (P<0,05). Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05) in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.

Acute exercise and caffeine improve insulin-induced hypoglycemia in normal and malnourished rats / Exercício agudo e cafeína melhoram a hipoglicemia induzida por insulina em ratos normais e desnutridos

In food restriction, hypoglycemic episodes can be more severe and persistent. This study assessed the influence of acute exercise and caffeine on the insulin-induced hypoglycemia in freely-fed or malnourished (50% food restriction) young rats. At the age of 60 days, rats under overnight fasting received an insulin injection to cause an episode of hypoglycemia. In some animals, hypoglycemia was preceded by an acute session of exercise, in others, caffeine was orally given 15 minutes after insulin injection; or exercise and caffeine were combined. Blood samples were collected at regular intervals for five hours after insulin injection. A beneficial effect of both exercise or caffeine on the hypoglycemic episode in the malnourished rats was found. In the control rats, the association of exercise+caffeine was more beneficial than either intervention alone. It is discussed that exercise and caffeine, alone or combined, can be used as exogenous anti-hypoglycemic resources, but considering the nutritional status of the subject.

Na restrição alimentar, os episódios de hipoglicemia podem ser mais severos e persistentes. Este trabalho avaliou a influência do exercício agudo e da cafeína sobre a hipoglicemia induzida por insulina em ratos jovens alimentados livremente ou desnutridos (50% de restrição alimentar) desde o nascimento. Aos 60 dias de idade, os ratos em jejum noturno receberam injeção de insulina para causar um episódio de hipoglicemia. Em alguns animais, a hipoglicemia foi precedida por sessão aguda de exercício; em outros foi administrada a cafeína via oral, 15 min. após a injeção de insulina; ou foi associada a exercício e cafeína. Amostras de sangue foram coletadas em intervalos regulares por 5h desde a aplicação da insulina. Registrou-se efeito benéfico do exercício e da cafeína isolados sobre o episódio hipoglicêmico nos ratos desnutridos. Nos ratos controle, a associação de exercício+cafeína teve efeito benéfico mais acentuado do que as intervenções separadas. É discutido que exercício físico e cafeína, isolados ou combinados, podem ser explorados como recursos anti-hipoglicêmicos exógenos, levando-se em consideração porém o estado nutricional do indivíduo.

Blood glucose regulation during fasting in rats under food restriction since birth

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 percent 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.

Desenvolvimento corporal e adiposidade de ratos Wistar submetidos a diferentes regimes alimentares / Development and adiposity of Wistar rats under different feeding regimens

Este trabalho avaliou o desenvolvimento de ratos submetidos a restrição alimentar (RA), seguida por alimentação livre. Foram feitos 3 grupos: controle (GC); RA na lactação (GRL); e RA até 60 dias com realimentação por 30 dias (GRR). O peso corporal do GRL sempre foi menor que o do GC, e a alimentação livre para o GRR não foi suficiente para ganho de peso compensatório completo. O peso relativo dos órgãos nos grupos que passaram por RA foi maior do que no GC, mas o peso relativo dos depósitos lipídicos foi: GC>GRL>GRR. A RA seguida de realimentação neste estudo não gerou indícios de obesidade.

This work evaluated the development of rats subjected to food restriction (FR) followed by free feeding. Three groups were designed: control (GC), FR during lactation (GRL), and FR until 60 days of age followed by free feeding for the next 30 days (GRR). Body weight of GRL was always lower than that of GC, and the free feeding of GRR was not long enough for complete compensatory body weight gain. The relative weight of the organs in the groups undergoing FR was higher than on GC, but the relative weight of the fat depots was GC>GRL>GRR. The FR followed by free feeding in this study did not create evidence of obesity.