Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of progressive, diabetes-associated adiposity on reproductive tract structure and function was examined in 4- to 16-week-old C57BL/KsJ, control (+/?) and diabetic (db/db) mice. Uterine and ovarian tissues were analyzed by transmission electron microscopy for ultrastructural changes associated with increased intracellular lipid accumulation. In addition, the same tissues were analyzed for changes in activity of tissue lipoprotein lipase, an enzyme that hydrolyzes lipoprotein-associated triacylglycerols and supports the cellular uptake and storage of free fatty acids. Between 8 and 16 weeks of age, intracellular lipid deposits increased dramatically in the ovarian granulosa, thecal and stromal cell populations, as well as in the uterine epithelium, of diabetic mice compared to controls. By 16 weeks of age, the lipid deposits essentially occupied the entire cytoplasmic area of both the ovarian and uterine cell types in diabetics. The basal lamina underlying the uterine epithelium was expanded in the diabetics relative to controls, and the hyperglycemic condition induced an observable increase in endometrial intercellular space that was occupied by a hyaline type of ground substance of unknown composition and origin. In association with these structural changes, both ovarian and uterine lipase activities were greatly increased in the db/db mice compared with controls. These data suggest that the structural adiposity and functional decline in reproductive tract condition of the db/db mutants are related to the enhanced cellular lipid deposition observed in this species. These changes in structural and metabolic parameters are related to the reproductive incompetence characteristic of this murine model.
Anat Rec 1986 Nov
PMID:Ultrastructural and metabolic changes associated with reproductive tract atrophy and adiposity in diabetic female mice. 378 18

The effects of the diabetes (D) mutation on utero-ovarian structure and function were examined in match-paired D and control (C) C57BL/KsJ mice between 2 and 16 weeks of age. Between 4 and 8 weeks of age, the uterine epithelium of D mice exhibited a remarkable increase in the amount of cytoplasmic lipid stores as compared with that of C animals. Associated with progressive hyperglycemia between 8 and 16 weeks of age, uterine atrophy and continued lipid accumulation occurred. Both serum progesterone and estradiol levels were lower in D than C mice between 8 and 16 weeks of age. In addition, the uteri of D mice failed to accumulate as much 3H-estradiol as C uteri at 16 weeks of age. These data demonstrate that changes in uterine structure that are attributable to depressed ovarian activity in diabetics underlie the reproductive failure in these animals. The temporal association between the onset of reproductive tract involution and the expressed hyperglycemic condition suggests a causal association between these events in the genetically diabetic C57BL/KsJ mouse.
Anat Rec 1985 Apr
PMID:Diabetes-associated alterations in uterine structure in the C57BL/KsJ mouse: relationship to changes in estradiol accumulation, circulating ovarian steroid levels, and age. 399 90

Progressive, diabetes-associated ovarian atrophy was analyzed in C57BL/KsJ diabetic (db/db) and control (+/?) mice between 2 and 16 weeks of age. Tissue changes were histologically and morphometrically analyzed and compared with ovarian functional indices (i.e., serum estradiol and progesterone) and metabolic (i.e., glucose uptake and estradiol sequestration) parameters. No significant differences were found between the ovarian follicular populations of either group at 2 and 4 weeks of age. However, between 4 and 8 weeks, the ovaries of diabetic mice exhibited marked stromal and follicular degeneration and an associated decline in the population of viable follicles as compared with controls. Between 8 and 16 weeks of age the follicular atrophy in the diabetics became more marked, as compared with controls, with the accumulation of intracellular lipid pools accenting the tissue degeneration and adiposity observed in both follicular and stromal compartments. In addition, ovarian function was depressed after 6 weeks of age in diabetic females as compared with controls as indicated by lowered serum estradiol and progesterone levels. Ovarian glucose uptake was enhanced in diabetic females while the ability of the ovary to sequester radiolabeled estradiol declined between 4 and 16 weeks of age as compared with controls. These data indicate that ovarian dysfunction in the (db/db) mutant mouse is associated with follicular atrophy, adiposity, impaired steroidogenesis, and imbalanced glucose utilization. These events occur in temporal association with the onset and progressive exacerbation of the hyperglycemic condition. It is suggested that ovarian involution in these mutants is directly related to an impaired follicular ability to metabolize properly the elevated intracellular glucose concentrations that develop in the (db/db) mice as compared with controls.
Anat Rec 1985 Apr
PMID:Morphometric evaluation of diabetes-associated ovarian atrophy in the C57BL/KsJ mouse: relationship to age and ovarian function. 399 93

Studies utilizing animal models of diabetes suggest that diabetic complications of impotence involve structural lesions in the testis as part of an overall defect in the pituitary-testicular axis. In the present study testicular biopsies from ten oligospermic and/or impotent men with diabetes were evaluated by light and electron microscopy. One biopsy was judged normal. The remaining tissue showed variable testicular pathology ranging from minimally to grossly affected. Seminiferous tubules had decreased tubule diameters, hyalinized tubule walls, and occluded lumina owing either to epithelial encroachment or cellular debris and exfoliated round germ cells. Sertoli cells were vacuolated and showed a high degree of apical cell membrane redundancy and degeneration. Although Sertoli-Sertoli cell junctional complexes appeared normal, Sertoli junctional specializations associated with spermatids were structurally abnormal or absent. All tubules were variably depleted of adluminal compartment germ cell types. The interstitial compartment was filled with a collagen-rich extracellular matrix concentrated around small blood vessels and seminiferous tubule walls. Capillaries and lymphatic endothelia appeared structurally abnormal and compromised by the interstitial "matrix expansion." Some Leydig cells contained a variable number of small to large lipid droplets, vacuoles, and secondary lysosomes. Results indicate the presence of tissue pathology in testes of impotent diabetic men. Discrete ultrastructural lesions in apical Sertoli cell cytoplasm are associated with spermatogenic disruption and morphological changes in the interstitial compartment suggest microvascular complications.
Anat Rec 1985 Sep
PMID:Interstitial compartment pathology and spermatogenic disruption in testes from impotent diabetic men. 407 61

The ketone body B-hydroxybutyrate (B-OHB) produces malformations and ultrastructural alterations in mitochondria of mouse embryos exposed for 24 hours to the compound in whole embryo culture. The present study was conducted to establish the time-course of the mitochondrial changes to determine whether the changes are reversible, and to relate these changes to the malformations produced by the compound. Since mitochondria also play a key role in the metabolism of ketone bodies, the capacity of the early somite embryo to metabolize B-OHB was investigated in an effort to link the morphological alterations in the mitochondria to a biochemical process. Early somite embryos were cultured 4, 8, or 24 hours in the presence of 32 mM DL-B-OHB and then cultured for an additional 24 hours in control serum. Finally, embryonic tissue during the teratogenic period was assessed for its capability to oxidize B-OHB using D-(3-14C)-B-OHB. The treated embryos showed progressive alterations in the mitochondria, beginning at 4 hours with a loss of matrix density and culminating at 24 hours with high-amplitude swelling, complete loss of matrix density, and disappearance of cristae. These alterations were reversible following removal of the embryos after 24 hours of exposure to B-OHB and culturing for an additional 24 hours in control serum. Metabolism studies demonstrated that the early somite embryo possesses a limited capacity to oxidatively metabolize B-OHB. The biochemical implications of these findings are discussed with respect to the possible role of ketone bodies in the mechanism of diabetes-induced congenital malformations.
Anat Rec 1985 Sep
PMID:Mitochondrial alterations in embryos exposed to B-hydroxybutyrate in whole embryo culture. 407 66

The effect of the progressive hyperglycemic condition on ovarian follicular maturation was studied in control, moderate (160-350 mg/dl blood glucose), and overt (greater than or equal to 350 mg/dl blood glucose), spontaneously diabetic Chinese hamsters. Match-paired (age, sex, and weight) control and diabetic animals were sacrificed at specific intervals during the development of the diabetic condition; the ovaries were collected and morphometrically analyzed for changes in ovarian follicular growth relative to blood glucose levels. Follicles were classified according to size, number, and condition. The total number of primary (100-200 micrometers diameter) and secondary (200-350 micrometers diameter) follicles was reduced in both moderate and overt diabetic females as compared with controls. The percentage of viable (i.e., nonatretic) follicles was greatly reduced in the secondary follicle class of overt diabetic animals as compared with controls. No significant differences were observed in the numbers of viable tertiary (i.e., greater than or equal to 350 micrometers diameter) follicles in any of the diabetic animals as compared with controls. The percentage of atretic, secondary follicles was greatly increased in the overt diabetic group as compared with controls. These data indicate that the progressive hyperglycemia associated with diabetes in the Chinese hamster induces a severe depression of normal follicular recruitment resulting in an impaired reproductive performance in this species.
Anat Rec 1984 Nov
PMID:Effects of progressive hyperglycemia on ovarian structure and function in the spontaneously diabetic Chinese hamster. 652 90

Alloxan is known to induce diabetic renal changes as well as causing nephrotoxic alterations. However, no ultrastructural study has been performed to differentiate diabetic verses toxic affects of alloxan to the tubule and/or glomerulus. Therefore the present study used the "protected" kidney model to prevent one kidney from being exposed to the alloxan while allowing the other to receive the drug immediately. In all experimental animals the right renal hilum was gently occluded for 5 minutes and then released. This was performed prior to the injection of alloxan. Subsequently, the left renal hilum was occluded at the time of, and for 5 minutes after, alloxan administration (40 mg/kg i.v.). The experimental rats were divided into three groups: untreated diabetics, diabetics treated with protamine-zinc-insulin, and alloxan-treated rats that failed to become diabetic. Three groups of controls were included: one group received an equal volume of saline diluent as the experimental rats but no clamping of either renal hilum; another group received the saline and had the left renal hilum occluded for 5 minutes; and a third group had both the right and left renal hila occluded. All animals were followed and sacrificed after 9 weeks. Endogenous creatinine clearance did not change among groups. Alloxan-treated nondiabetic rats displayed marked interstitial nephritis in unprotected kidneys, while protected kidneys were normal. The diabetic state resulted in mesangial proliferation and focal glomerular basement membrane thickening as well as glomerular capillary endothelial abnormalities and visceral epithelial foot-process fusion. The endothelial changes consisted of focal areas showing a reduction in the size of endothelial fenestrae. All glomerular changes were ameliorated by insulin treatment. We conclude: 1) alloxan per se is distinctly nephrotoxic; and 2) the glomerular endothelium and epithelium are involved early in the course of experimental diabetes.
Anat Rec 1984 Jan
PMID:The effect of alloxan, and alloxan-induced diabetes on the kidney. 671 36

The noradrenergic sympathetic innervation of the penis of control and 4-month streptozotocin-diabetic rats was examined with the glyoxylic acid histofluorescence method. Noradrenergic varicosities were found in the corpora cavernosa in a dense subtunical plexus and in the perisinusoidal and trabecular regions of the erectile tissue, in the corpus spongiosum in perisinusoidal tissue, around large arteries and veins, and around small tortuous arterioles and small draining veins of the corpora cavernosa and spongiosum. Noradrenergic varicosities were diminished in number and fluorescent intensity in all regions of the penis of diabetic rats compared with controls. The subtunical plexus was absent, perisinusoidal and trabecular varicosities were sparse, and only occasional intermittent, discontinuous, dull fluorescent fibers or plexuses were found around the vessels. Quantitation with high-performance liquid chromatography revealed a significant reduction of norepinephrine in the penis of diabetic rats compared with controls. The present study suggests that long-term streptozotocin diabetes in the rat is accompanied by sympathetic autonomic neuropathy of the penis that seems to parallel changes in the noradrenergic content of penile corpora of men with diabetes and erectile impotence. The streptozotocin-diabetic rat merits further study to explore the relationship between noradrenergic innervation of the penis and erectile tissue.
Anat Rec 1983 May
PMID:Noradrenergic innervation of the penis in control and streptozotocin-diabetic rats: evidence of autonomic neuropathy. 688 50

Although there is a recent increase in the use of the isolated pancreatic islets of the rat in the transplantation and functional studies, there has been no detailed quantitative assessment on the size and cellular constituents of islets after the isolation procedure. The present work was undertaken to study the size classes of the isolated islets and the morphometry of their cellular populations. Islets of the rat pancreas were isolated by using the intraductal collagenase digestion technique, the most commonly used procedure for the isolation of pancreatic islets. Different endocrine cells of the isolated islets were stained by immunoperoxidase staining techniques. The distribution of the cellular constituents of the isolated islets was similar to that of the intact islets of the normal pancreas; A, D, and PP cells were peripherally arranged around the centrally located B cells. However, morphometric quantitative study showed that the percent volume and percent number of A, D, and PP cells of the isolated islets were lower than those of the corresponding intact ones. Further, the mean true diameter of the isolated islets was lower than that of the intact ones. These data indicate loss of islet cells during the process of isolation. Most of the lost cells were from the periphery of islets. This may provide an explanation for the incomplete metabolic control and recurrence of hyperglycemia encountered after isolated islet transplantation in the treatment of diabetes mellitus. It seems that further refinements of the isolation techniques are necessary to obtain islet tissue with total cellular integrity, before a complete success in transplantation could be achieved.
Anat Rec 1993 Dec
PMID:Isolated pancreatic islets of the rat: an immunohistochemical and morphometric study. 790 7

Measurements of serum fructosamine and glycated haemoglobin are increasingly used to complement plasma glucose concentration in the fasting dog to diagnose diabetes mellitus and to monitor the response to treatment. These measurements are not affected by acute changes in the glucose concentration and reflect the average plasma glucose concentration over the preceding one to two weeks in the case of serum fructosamine and two to three months in the case of glycated haemoglobin. Both components can be measured in canine blood samples, but glycated haemoglobin is still not measured routinely; however, the serum fructosamine concentration can be measured accurately by means of simple spectrophotometric assays. The sensitivity and specificity of serum fructosamine in diagnosing diabetes mellitus in dogs with clinical signs of the disease are very high (0.93 and 0.95, respectively). Furthermore, serum fructosamine can be used as a reliable screening test to identify diabetic dogs in an average middle-aged to older hospital population. In addition, serum fructosamine can distinguish between hyperglycaemic non-diabetic dogs and hyperglycaemic diabetic dogs. Preliminary data suggest that therapy can be safely monitored and regulated on the basis of serial measurements of the serum fructosamine concentration in diabetic dogs.
Vet Rec 1995 Oct 14
PMID:Glycated blood proteins in canine diabetes mellitus. 854 38


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