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Ciglitazone, a new hypoglycaemic agent. 4. Effect on pancreatic islets of C57BL/6J-ob/ob and C57BL/KsJ-db/db mice (1984)

Diani, A. R. ; Peterson, T. ; Sawada, G. A. ; [et al.]

Springer

Diabetologia 27 (1984), S. 225-234

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ISSN: 1432-0428

Keywords: Ciglitazone ; C57BL/6J-ob/ob mice ; C57BL/KsJ-db/db mice ; β-cell granulation ; electron microscopy ; rough endoplasmic reticulum ; Golgi apparatus

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Summary Pancreases of treated and control male C57BL/6J-ob/ob and C57BL/KsJ-db/db mice were evaluated by qualitative and morphometric microscopic techniques to determine the effects of chronic ciglitazone treatment on the morphology of β cells and surface area and number of pancreatic islets. The β cells of treated ob/ob and db/db mice displayed moderate to heavy granulation whereas most β cells of untreated obese and diabetic mice were extensively degranulated. Although moderate proliferation of the rough endoplasmic reticulum and Golgi apparatus was evident in some β cells of treated db/db mice, both groups of treated ob/ob and db/db mice displayed an improved pattern of insulin synthesis and storage. In contrast, the β cells of untreated ob/ob and db/db mice were in a severe state of stress which was indicated by extensive hypertrophy of the rough endoplasmic reticulum, Golgi apparatus and mitochondria. Some β cells of untreated db/ db mice also displayed lysosome aggregates indicative of early stages of necrosis. Morphometric analysis revealed that the surface area of islets of treated ob/ob mice was significantly smaller in comparison with that of untreated ob/ob mice. Since the surface area of islets of treated C57BL/6J-+/? mice (lean littermates of ob/ob mice) was less than that of treated ob/ob mice, the progression of islet hypertrophy in the obese mice was probably arrested or attenuated but not to the level of the treated +/? mice. The number of pancreatic islets was significantly greater in treated than in untreated db/ db mice. A majority of the islets of untreated db/db mice were atrophie and consisted of acinar and endocrine cells whereas most of the islets of treated db/db mice appeared to be intact and unremarkable. The results of this study suggest that ciglitazone is an effective hypoglycaemic agent which may directly or indirectly promote β-cell regranulation and an improved pattern of insulin synthesis and storage in ob/ob and db/db mice. However, in treated db/db mice, there still was some evidence of stress in the β cells. Overall, the prolonged treatment with ciglitazone also seemed to inhibit the hypertrophy of islets in ob/ob mice and protect the structural integrity and viability of islets in db/db mice.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00273811

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Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer (1995)

Barnes, Stephen ; Peterson, T. Greg ; Coward, Lori

New York, N.Y. : Wiley-Blackwell

Journal of Cellular Biochemistry 59 (1995), S. 181-187

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ISSN: 0730-2312

Keywords: Animal models ; delivery choice ; genistein ; mechanisms ; soy ; Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Pharmacologists have realized that tyrosine kinase inhibitors (TKI) have potential as anticancer agents, both in prevention and therapy protocols. Nonetheless, concern about the risk of toxicity caused by synthetic TKIs restricted their development as chemoprevention agents. However, a naturally occurring TKI (the isoflavone genistein) in soy was discovered in 1987. The concentration of genistein in most soy food materials ranges from 1-2 mg/g. Oriental populations, who have low rates of breast and prostate cancer, consume 20-80 mg of genistein/day, almost entirely derived from soy, whereas the dietary intake of genisteinin in the US is only 1-3 mg/day. Chronic use of genistein as a chemopreventive agent has an advantage over synthetic TKIs because it is naturally found in soy foods. It could be delivered either in a purified state as a pill (to high-risk, motivated patient groups), or in the form of soy foods or soy-containing foods. Delivery of genistein in soy foods is more economically viable ($1.50 for a daily dose of 50 mg) than purified material ($5/day) and would require no prior approval by the FDA. Accordingly, investigators at several different sites have begun or are planning chemoprevention trials using a soy beverage product based on SUPROTM, an isolated soy protein manufactured by Protein Technologies International of St. Louis, MO. These investigators are examining the effect of the soy beverage on surrogate intermediate endpoint biomarkers (SIEBs) in patients at risk for breast and colon cancer, defining potential SIEBs in patients at risk for prostate cancer, and determining whether the soy beverage reduces the incidence of cancer recurrence. These studies will provide the basis for formal Phase I, Phase II and Phase III clinical trials of genistein and soy food products such as SUPROTM for cancer chemoprevention.