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G C Gerritsen

Publications and source records attributed to G C Gerritsen.

At least 19 recordsLinked to original sources
PubMed1988

Reduced hypothalamic somatostatin and neuropeptide Y concentrations in the spontaneously-diabetic Chinese hamster.

Hypothalamic concentrations of six regulatory peptides having central effects on appetite and/or glucoregulation were measured by radioimmunoassay in spontaneously-diabetic Chinese hamsters and in age- and sex-matched non-diabetic control animals. In the diabetic hamsters, hypothalamic concentrations of somatostatin and neuropeptide Y were significantly reduced by 25-30% below controls. None of the other four peptides examined (bombesin, galanin, neurotensin and vasoactive intestinal peptide) differed significantly between the two groups. Disturbances in neuropeptide Y (the most potent central appetite stimulant yet discovered) and in somatostatin could be related to hyperphagia, an early and possibly primary abnormality of the diabetic syndrome in the Chinese hamster.

Animals↗
PubMed1988

Tissue norepinephrine concentration in spontaneously diabetic Chinese hamsters.

There is some controversy concerning a possible effect of diabetes mellitus on the sympathetic nervous system in humans with spontaneous diabetes mellitus and in animals with experimental diabetes mellitus. In this study we compared the tissue norepinephrine (NE) concentration of normal and diabetic Chinese hamsters in the untreated state and after treatment with insulin. Diabetes resulted in a 128% increase in the NE concentration of the kidney in female but not male hamsters. The NE concentration was increased in the liver (133%) and in the cerebral cortex (118%) of both male and female hamsters. There was no significant increase in the NE concentration of hypothalamus, acinar pancreas, pancreatic islets, or heart of diabetic hamsters. Three days of insulin therapy reduced the elevated NE concentration in kidney, liver and cerebral cortex of diabetic hamsters to the levels found in normal hamsters. However, insulin therapy of normal hamsters did not reduce the tissue NE concentration of the kidney, liver, and cerebral cortex below the normal levels found in these animals. Insulin therapy reduced the hypothalamic concentration of NE in both diabetic and normal hamsters. The increase in kidney NE concentration in female diabetic hamsters was not due to a reduction in renal size, for the kidneys of both female and male diabetic hamsters were larger than those of normal hamsters. When synthesis of NE was inhibited with alpha-methyltyrosine, there was a comparable rate of fall in the tissue NE concentration in the four experimental groups, suggesting that the increased tissue NE concentration in the tissues of diabetic hamsters was not due to a decreased rate of disappearance of this compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The influence of plasma insulin concentrations on tissue insulin levels in rodents: a study of the diabetic Chinese hamster and the ob/ob mouse.

Immunoreactive insulin was measured in acid-ethanol extracts of kidney, brain, liver, and heart from genetically diabetic Chinese hamsters and their nondiabetic controls and from obese (ob/ob) mice and their thin littermates. Selected samples were filtered on Sephadex G-50 columns and the insulin concentration determined. There was a good correlation between the insulin level measured in the acid-ethanol extracts of tissues and the insulin level after gel filtration, suggesting that the concentration measured in the whole extract is representative of the true insulin content. The present data demonstrate that different extrapancreatic organs contain characteristic amounts of insulin that are often (sometimes several-fold) higher than the insulin level of plasma. The tissue insulin concentrations also exhibit a wide range of values, with occasional high values. The data also show a direct correlation between plasma and kidney insulins but no relationship between plasma and brain insulins and a mixed correlation among plasma and liver and heart insulins.

Animals↗
PubMed1986

Systematic evaluation of microangiopathy in diabetic Chinese hamsters. I. Morphometric analysis of minimal glomerular basement membrane thickness in 11- to 15- and 19- to 23-month-old Chinese hamsters.

Renal glomeruli of 11- to 15- and 19- to 23-month-old nondiabetic (M) and diabetic (XA and AC) genetic sublines of Chinese hamsters were morphometrically analyzed to determine if minimal capillary basement membrane thickening (CBMT) is a microvascular complication in this animal model. Minimal glomerular capillary basement membrane thickness was significantly elevated in the AC diabetic subline (117.2 nm +/- 5.0, P less than 0.004) compared with the M nondiabetic subline (99.0 nm +/- 14.0) in the 11- to 15-month age span. However, in the 19- to 23-month age range, both the XA (140.2 nm +/- 20.0, P less than 0.02) and AC (140.1 nm +/- 12.4, P less than 0.04) diabetic sublines displayed significantly greater glomerular capillary basement membrane thickness in comparison with the M nondiabetic subline (119.0 nm +/- 13.4). The greatest influence on CBMT in the diabetics was shown to be a combination of the aging process and severity of hyperglycemia. This initial systematic morphometric study has demonstrated that glomerular CBMT is a characteristic microvascular lesion in 11- to 15-month-old diabetic AC and 19- to 23-month-old diabetic XA and AC Chinese hamsters in comparison with age-matched nondiabetics. Furthermore, this investigation suggests that the Chinese hamster appears to be an acceptable model for the study of chronic complications associated with diabetic nephropathy.

Age Factors↗
PubMed1986

Morphometric evaluation of capillary basement membrane thickness in the quadriceps muscle of diabetic and nondiabetic Chinese hamsters.

Quadriceps muscle capillaries from 19-23 month old genetically diabetic (XA and AC) and nondiabetic (M) subline Chinese hamsters were morphometrically evaluated to determine if capillary basement membrane thickening (CBMT) is a quantifiable complication of diabetes. Significant CBMT was present in the diabetic XA Chinese hamsters (49.37 nm +/- 17.81, p less than 0.007) in comparison with the nondiabetic M hamsters (34.08 nm +/- 9.98). Although there was a trend towards expansion of the muscle capillary basement membranes in the diabetic AC Chinese hamsters, the value was not statistically significant. A nested analysis of variance showed that the greatest source of variation in basement membrane thickness occurred among capillaries within each animal. In addition, a positive correlation (r = 0.62; p less than 0.002) existed between blood glucose levels and CBMT in the XA subline. These data should serve as guidelines for evaluation of antimicrovascular disease compounds which will be tested to determine if they prevent or retard microangiopathy in the diabetic Chinese hamster.

Animals↗
PubMed1985

Elevated levels of vasoactive intestinal peptide in the eye and urinary bladder of diabetic and prediabetic Chinese hamsters.

The eyes and urinary bladder of non-diabetic, prediabetic and diabetic Chinese hamsters were evaluated by radioimmunoassay and immunocytochemistry to determine the content and distribution of vasoactive intestinal peptide (VIP). The average concentration of VIP was increased in the eyes of all diabetic (pmol/g = 68%, pmol/organ = 50%) and prediabetic (pmol/g = 152%, pmol/organ = 115%) hamsters compared with age-matched non-diabetic animals. Immunocytochemistry showed that the elevation of VIP was primarily related to greater intensity of fluorescence of the nerve fibres in the vasculature of the choroid. The average content of VIP in the urinary bladder was greater in diabetic animals only on the basis of pmol/organ (135%) and in prediabetics on the basis of pmol/g (87%) compared with non-diabetic animals. Qualitative immunocytochemistry suggested that the elevated level of VIP was related to a larger distribution of nerve fibres in the urinary bladder of diabetic hamsters. The high level of VIP in the eyes and urinary bladder of diabetic and prediabetic hamsters is an interesting observation which should receive further study to determine whether it is an aetiological agent underlying the pathogenesis of ophthalmic complications and neurogenic bladder or the result of some pathological process which affects these organs.

3-Hydroxybutyric Acid↗
PubMed1985

Effect of antilymphocyte serum and neonatal thymectomy upon onset of diabetes in the Chinese hamster.

Prediabetic Chinese hamsters were treated with antilymphocyte serum (ALS), or thymectomized in order to test the hypothesis that beta-cell loss leading to diabetes in this animal model was related to cell-mediated autoimmunity. In addition, passive transfer of diabetes from the Chinese hamster to the nude mouse was attempted by transplantation of lymphocytes. Treatment of prediabetic Chinese hamsters with ALS or thymectomy did not alter development or severity of diabetes in this animal model. Lymphocytes from newly diagnosed diabetic Chinese hamsters did not cause hyperglycemia in nude mice. These three lines of evidence suggest that cell-mediated autoimmunity does not contribute to the etiology of diabetes in the Chinese hamster. The Chinese hamster remains a good model for the study of those forms of diabetes not related to cell-mediated autoimmune phenomena.

Animals↗
PubMed1984

Insulin, glucagon, and somatostatin release from the prediabetic Chinese hamster.

Diabetes mellitus in the adult Chinese hamster is characterized by subnormal pancreatic insulin release in vitro, decreased insulin content, and lack of obesity. The cause of the islet B-cell failure is not clear. We measured insulin, glucagon, and somatostatin release from in vitro perfused pancreases of young (mean age 10 and 20 weeks), genetically diabetic animals (subline AC, mean plasma glucose 8.0 and 16.6 mmol/l, respectively). Compared to age- and sex-matched normal hamsters (subline M, mean plasma glucose 5.3 mmol/l), the younger diabetic animals had a significantly elevated mean plasma glucose level, but net in vitro pancreatic release of insulin, glucagon, and somatostatin was normal. Pancreatic content of insulin and glucagon was also not significantly different from normal. At age 20 weeks, when the plasma glucose of the diabetic animals was even more elevated, pancreatic content and release of insulin were significantly subnormal, whereas glucagon and somatostatin release were normal, and pancreatic content of glucagon was normal. In a similar group of young (mean age 10 weeks) diabetic animals, non-fasting plasma insulin levels were within the normal range, but the corresponding glucose levels were excessive in most of the animals (13 out of 19). In conclusion, 10-week-old diabetic hamsters show mild hyperglycaemia which cannot be accounted for directly by decreased pancreatic release in response to a glucose plus arginine stimulus in vitro. Decreased ability of the B cell to respond in vivo to hyperglycaemia or peripheral resistance to insulin may contribute to later B-cell failure in the older diabetic hamster.

Aging↗
PubMed1984

Feeding systems in Chinese hamsters.

Modulation of feeding by opiates, putative satiety peptides, and dopamine was explored in the Chinese hamster, an animal that develops diabetes mellitus in certain inbred strains. Diabetic hamsters were hyperphagic relative to their nondiabetic controls, but both groups exhibited natural circadian variation in feeding. Starvation provoked hyperphagia of about 1-h duration in both groups. Naloxone and butorphanol had no effects on Chinese hamster feeding. Opiate receptor binding on Chinese hamster brains demonstrated no specific binding of naloxone or ethylketocyclazocine, but IR-dynorphin concentrations were comparable with that in rats. N-allylnormetazocine, a sigma-opiate receptor agonist, appeared to stimulate diabetic hamster feeding. Peptides reputed to have satiety effects in rats were without effect in Chinese hamsters: cholecystokinin, bombesin, somatostatin, and pancreatic polypeptide. Calcitonin limited feeding in both groups but may be nonspecific. Dopaminergic blockade by haloperidol also limited feeding, and diabetic hamsters were more sensitive to this. Although Chinese hamsters clearly can modulate their food intake when diabetic, we conclude that the opiatergic and peptidergic influences on feeding are very different from those in rats and may be of little importance.

Animals↗
PubMed1984

Deficient humoral antibody response of the spontaneously diabetic Chinese hamster.

The antibody responses of spontaneously diabetic Chinese hamsters to sheep erythrocytes was investigated. After primary challenge, total antibody production of the diabetics was only 50% or less than that of nondiabetic controls, and little or no switchover to IgG production occurred. After second challenge, total antibody of diabetics was still reduced compared with controls. Some switchover to IgG did occur after second challenge but was only 40% that of controls. Poor antibody response was not related to abnormal glucose metabolism since low titers and lack of IgG was found in euglycemic prediabetics. Additionally, genetic nondiabetics rendered hyperglycemic by streptozotocin responded normally, similar to euglycemic controls. The impaired humoral antibody response of the diabetic hamster is similar to that reported for some human diabetics and makes this animal model attractive for studying the consequences and possible causes of diabetes-dependent impairment of immune responses.

Animals↗
PubMed1982

Morphometric evaluation of the hypothalamic-ovarian axis of the ketonuric, diabetic Chinese hamster: relationship to the reproductive cycle.

The relationship between diabetes and the morphological alterations which occur in hypothalamic and ovarian tissue was examined in the long-term, ketonuric-diabetic Chinese hamster. Matched diabetic and non-diabetic control hamsters were inspected daily for changes in the reproductive cycle by vaginal lavage. On dioestrus, animals were perfused, the hypothalamus and ovaries collected, prepared for microscopy and morphometrically analyzed. The nuclei in the medial basal hypothalamus of diabetic hamsters exhibited a decreased area (p less than 0.01) and neuronal population (p less than 0.05-0.01) compared with controls. The ovaries of the diabetic animals had a reduced follicular population (p less than or equal to 0.05) and an increased atresia rate (p less than or equal to 0.05) compared with controls. In addition, all diabetic hamsters were acyclic. In diabetic animals, the corpora luteal cells contained a reduced lipid content (p less than or equal to 0.001) which was possibly functionally related to a significant decline in serum progesterone levels (p less than or equal to 0.01). Based on these results it is suggested that the hypothalamic-ovarian axis is both morphologically and functionally impaired in the diabetic hamster.

Animals↗
PubMed1982

Peripheral neurology of the diabetic Chinese hamster.

Genetically diabetic Chinese hamsters were examined anatomically and physiologically for evidence of peripheral neuropathy. Control animals were from non-diabetic strains. Conduction velocities in both motor and sensory components of the hind limb nerves were reduced 16-22% in diabetic compared with control hamsters. However, there was no reduction in nerve fibre diameters or other signs of abnormal morphology that could be correlated with these physiological effects. It is concluded that the diabetic hamster is useful as a model of human diabetic peripheral neuropathy, but the analogy is not precise. The neuropathy of moderately diabetic hamsters is generally less severe than human diabetic neuropathy in its clinical stages.

Animals↗
PubMed1982

Depopulation of the ventromedial hypothalamic nucleus in the diabetic Chinese hamster.

The relationship between diabetes and the size, density and area of the ventromedial hypothalamic nucleus (VMH) was studied in the genetically diabetic Chinese hamster. Matched diabetic and non-diabetic control chinese hamsters were perfused, the hypothalamus collected, sectioned and stained for light microscopy. The mid-point of each VMH nucleus was located, photographed and enlarged for morphometric analysis. Each neuron that possessed a nucleolus and was located within the confines of a VMH was counted, and subsequently the area of each nucleus and the density of neurons per area of VMH were calculated. The results indicated that both the area and absolute number of neurons within the VMH of diabetic hamsters were significantly reduced compared to control values (P less than 0.01) The density of neurons per unit area of VMH was similar in both groups. These data suggest that the VMH experiences a neuronal depopulation in diabetic hamsters which may have a functional influence on the hypothalamic-pancreatic axis in this species.

Animals↗
PubMed1982

The Chinese hamster as a model for the study of diabetes mellitus.

Selection for and against diabetes and subsequent inbreeding of Chinese hamsters started in 1963. Currently there are six inbred sublines that have greater than 85% incidence of glycosuria and two control inbred nondiabetic sublines that are essentially free of glycosuria. At birth, hamsters from inbred sublines are considered prediabetic. There is phenotypic variation between diabetic sublines. Onset time, incidence of ketonuria, blood glucose, plasma insulin, glucagon and glycohydrolase levels vary from subline to subline, but pancreatic insulin and glucagon levels are consistently low and high, respectively, in all diabetic sublines compared with nondiabetics. Experimental breeding data suggest a minimum of two homozygous recessive genes for diabetes. It is not known if the inbred lines are similar diabetic genotypes, but the probability is high that modifier background genes vary from subline to subline. Chinese hamsters have diabetes ranging from mild to severe. Animals weighing 25 g can excrete up to 75 ml of urine containing 3 g of glucose per day. Fasting blood glucose as high as 500 mg/dl and 10 mumol/ml of beta-hydroxybutyrate have been reported. Gluconeogenesis is elevated, and some glycolytic enzymes are decreased in severe diabetes. Low levels of renal acid glycohydrolase enzymes may contribute to glomerular capillary loop basement membrane thickening in diabetic hamsters. Caloric restriction per se or reduction of dietary fat prevented onset of hyperglycemia and hyperinsulinemia in prediabetics. Morphologic changes have been observed in pancreatic islets, kidney, nerve, blood vessels, eyes, brain, and genito-urinary systems of diabetic Chinese hamsters. Pathogenesis of diabetes in this animal appears to be related to an increased demand for insulin. Initially there is a positive response to this demand by beta cells, but exhaustion occurs. This is followed by a decrease in beta-cell mass and relative or absolute insulin deficiency.

Animals↗
PubMed1982

Metabolic and underlying causes of diabetes mellitus.

It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements. Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines.

Alloxan↗
PubMed1981

Morphometric analysis of autonomic neuropathology in the abdominal sympathetic trunk of the ketonuric diabetic Chinese hamster.

Fibers from the infradiaphragmatic portion of the sympathetic trunk of ketonuric diabetic Chinese hamsters were quantitatively analyzed by light and electron microscopy to determine frequency distribution and numerical density. Myelinated and unmyelinated fibers displayed a significant reduction in diameter which was exacerbated by increased duration of ketonuria. Mean numerical density of myelinated fibers was reduced whereas that of unmyelinated fibers was increased. The alterations in sympathetic nerve populations are believed to be a manifestation of previously observed demyelination and axonal degeneration. On the basis of axon diameter, it appeared that both visceral afferent and efferent fibers were affected. These data strongly suggest that autonomic neuropathology in the sympathetic trunk of the diabetic Chinese hamster may be a critical factor underlying gastrointestinal dysfunction.

Animals↗