Effectiveness of Per-Oral Insulin in Human Diabetes

Murlin, John R.; Gibbs, C. B. F.; Romansky, Monroe J.; Steinhausen, T. B.; Truax, Frederick L.

doi:10.1172/jci101175

Cited by 14 publications

(5 citation statements)

References 11 publications

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“…For decades, oral insulin delivery has been studied in humans and different experimental models (Murlin et al 1940, Florence 2015, Sheng et al 2016. Although the peptide insulin is destroyed in acid environment of stomach, by not completely understood means it promotes serum metabolic parameters improvement as well as promotes function and morphological changes in gut epithelium (Sukhotnik et al 2011, Shehadeh et al 2006.…”

Section: Introductionmentioning

confidence: 99%

Oral insulin improves metabolic parameters in high fat diet fed rats

Lipinski

Kmetiuk

Mathias

et al. 2017

An. Acad. Bras. Ciênc.

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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.

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Section: Introductionmentioning

confidence: 99%

Oral insulin improves metabolic parameters in high fat diet fed rats

Lipinski

Kmetiuk

Mathias

et al. 2017

An. Acad. Bras. Ciênc.

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“…Among the three routes, oral administration appears to be the more convenient, appropriate and certainly the most physiological, insulin being directly channelled from the intestine to the liver. Since the discovery of insulin attempts at oral administration have been made with differing amounts of effectiveness [17][18][19][20][21]. This is due to problems with the fact that insulin administered orally encounters the proteolytic activity of the gastrointestinal tract and the relative impermeability of the intestinal epithelium to the transport of peptides.…”

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confidence: 99%

Biochemical and morpho-cytochemical evidence for the intestinal absorption of insulin in control and diabetic rats. Comparison between the effectiveness of duodenal and colon mucosa

et al. 1994

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A combined biochemical and morpho-cytochemical investigation was carried out in order to assess insulin absorption by the duodenal and colon epithelium. Insulin was introduced in the lumen of the rat duodenum or colon in combination with sodium cholate and aprotinin. Blood analysis made at several time points has demonstrated a rapid increase in circulating levels of insulin followed by significant and consistent decreases in blood glucose. This indicates that biologically active insulin is absorbed by the intestinal mucosa and transferred to the circulation. Because of the initial high blood glucose levels, the lowering of the glycaemic values was more significant in diabetic animals. Also, levels of circulating insulin remained higher for longer time when the administration was performed in the colon. The integrity of the intestinal wall after insulin administration, evaluated morphologically, was retained. Application of protein A-gold immunocytochemistry has established the pathway for insulin absorption. In both duodenal and colon epithelial cells the labelling for insulin was detected in the endosomal compartment, in the Golgi apparatus and in association with the baso-lateral plasma membrane interdigitations. Some labelling was also present in the interstitial space and in capillary endothelial plasmalemmal vesicles. Insulin introduced in the lumen of the rat duodenum and colon appears thus to be rapidly internalized by the epithelial cells and transferred through a transcytotic pathway to the interstitial space from which it reaches the blood circulation. This exogenous insulin then induces significant decreases in plasma glucose levels which lasts for several hours. The results obtained support the possibility for the clinical development of an oral preparation of insulin.

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“…Inhibiting proteolytic activity might preserve insulin so that it can be absorbed. Murlin et al 2 found that an insulin solution with o.i per cent hydrochloric acid placed directly into the duodenum of diabetic patients could be absorbed and increase the utilization of glucose. When ioo U./kg.…”

Section: Discussionmentioning

confidence: 99%

Increase in Plasma Immunoreactive Insulin Following Administration of Insulin to the Gastrointestinal Tract of Rabbits

et al. 1972

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Changes in plasma insulin levels in response to enteral administration of insulin have been studied in rabbits.Insulin, when administered to the stomach, did not cause hypoglycemia at doses up to 150 U./kg. When insulin at doses over 40 U,/kg. was infused to the upper jejunum via an indwelling catheter, there was a slight but significant increase in plasma insulin levels, followed by a significant fall in blood glucose. A considerable increase in plasma insulin was observed when insulin at doses over 20 U./kg. was infused to the Thiry-Vella loop of the jejunum in which no pancreatic secretion entered. With a dose of 100 U./kg., the mean plasma insulin rose promptly to the peak of 241 /tU./ml., followed by a severe hypoglycemia.As judged by hypoglycemic and immunological responses, insulin can be absorbed from the intestine in a physiologically active form, but the fraction absorbed is relatively small. DIABETES 21: 203-208, April, 1972. A number of recent investigations either in vitro by the use of everted sac technic 1 or in vivo, has indicated that insulin can be absorbed from the small intestine of mammals in the presence of dyes, 2 saponins, 3 water-inoil-in-water emulsions 4 or proteolytic inhibitors. 1 ' 5 " 7 As a result, it has been held that insulin is not irreversibly altered and at least part of the hypoglycemic activity might be restored.To the best of our knowledge, there has been no systematic comparison made of the effects of insulin administered via the gastrointestinal tract and the serum insulin levels. To obtain additional information on the

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Effectiveness of Per-Oral Insulin in Human Diabetes

Cited by 14 publications

References 11 publications

Oral insulin improves metabolic parameters in high fat diet fed rats

Oral insulin improves metabolic parameters in high fat diet fed rats

Biochemical and morpho-cytochemical evidence for the intestinal absorption of insulin in control and diabetic rats. Comparison between the effectiveness of duodenal and colon mucosa

Increase in Plasma Immunoreactive Insulin Following Administration of Insulin to the Gastrointestinal Tract of Rabbits

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