IMMUNOTHERAPY FOR INSULIN-DEPENDENT DIABETES MELLITUS IN THE “BB” RAT

Life Sciences ◽  
1997 ◽  
Vol 61 (3) ◽  
pp. 283-291 ◽  
Author(s):  
James A Thliveris ◽  
Asher Begleiter ◽  
Deborah Manchur ◽  
James B Johnston
1991 ◽  
Vol 69 (3) ◽  
pp. 311-319 ◽  
Author(s):  
Fraser W. Scott ◽  
Errol B. Marliss

An international symposium on diet as an environmental factor in development of insulin-dependent diabetes mellitus (IDDM) was held in Ottawa, Ont., Canada, September 1989. Several environmental factors such as viruses and chemicals, as well as diet modifications per se, were reviewed in both human and animal diabetes. Although the pathophysiology in the BB rat and nonobese diabetic (NOD) mouse may have different immunological mechanisms, both these animal syndromes of spontaneous IDDM are markedly affected by diet. In them, cereal-based rodent diets are the most diabetogenic and hydrolyzed casein-based purified diets are least diabetogenic. In two different NOD mouse colonies, diabetogenicity of cereal-based diets can be markedly decreased by extracting the diet with chloroform–methanol or water, reflecting either the different composition of the diets used in each colony or the chemical extraction and (or) alteration of certain diabetogenic agents. Thus, dietary lipids can be potent immune system modulators in several systems and the role of chloroform–methanol soluble agents in initiation and (or) promotion of the disease process is being studied. Attention was focused on protein sources previously identified by some groups as diabetogenic such as skim milk powder and wheat products, both of which can be found in natural ingredient rodent feeds. Circulating antibodies to dietary antigens such as bovine serum albumin and (crude) wheat gliadin may be elevated in diabetes-prone rodents and newly diagnosed patients, but their relationship to the pathogenesis of IDDM remains to be established. Because diet components can clearly influence the expression of the diabetic syndromes in the BB rat and NOD mouse, it will be crucial to identify the chemical nature of such components as a first step in understanding their mode of action. The epidemiological evidence for a role of diet in human IDDM was reviewed and is sufficient to suggest an association, but more data are required and such studies are currently underway. The complexity of the search for diabetogens in various diet constituents may be compounded by possible interaction with infectious agents and the large amounts of material required for testing in whole animal feeding experiments. It was the aim of this conference to examine the diet–IDDM relationship from a variety of perspectives that may ultimately contribute in different ways to identification of diabetogenic agents in our diet and possibly a safe and inexpensive means of avoiding or substantially delaying development of clinical IDDM in susceptible individuals.Key words: diabetes, pathogenesis, diet, nutrition, prevention.


1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.


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