The Chinese Hamster as a Model for the Study of Diabetes Mellitus

Gerritsen, G. C.

doi:10.2337/diab.31.1.s14

Cited by 61 publications

(36 citation statements)

References 45 publications

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“…We chose a spontaneous diabetic hamster model, in which two sublines of different glycaemic levels have been created through breeding, one with mild and one with severe hyperglycaemia [11]. Previous studies established that the spontaneous diabetic hamster eventually develops some early features of diabetic retinopathy such as acellular capillaries and an increase in the capillary endothelial cell to pericyte ratio [12]. Using retinal digest preparations of animals with various durations of diabetes (3±12 months) we compared animals with mild and severe hyperglycaemia, measured retinal autofluorescent AGE and parameters of diabetic retinopathy such as pericyte loss and acellular capillaries.…”

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confidence: 99%

The relationship of glycaemic level to advanced glycation end-product (AGE) accumulation and retinal pathology in the spontaneous diabetic hamster

Hammes

Wellensiek

Klöting³

et al. 1998

Diabetologia

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The most characteristic findings of diabetic background retinopathy in humans are increased capillary permeability and progressive vascular occlusions. According to studies correlating angiographic in vivo findings with post-mortem retinal digests microaneurysms cluster around areas of capillary non-perfusion [1,2], possibly in an early abortive attempt at retinal new vessel formation. From earlier work it is known that pericytes may disappear leaving behind empty pockets in the capillary basement membrane [3]. Since endothelial cells do not leave behind such traces when they disappear, their fate during the initial course of retinal damage is uncertain, despite indication for both focal loss, leading to acellular capillaries, and focal proliferations leading to hypercellular vessels and microaneurysms [4,5]. Pericyte loss and acellular, occluded capillaries have been found in diabetic animals, in which the natural course of diabetic retinopathy has been studied [6,7]. Diabetologia (1998) Summary To assess the relationship between glucose and advanced glycation end products (AGE) and the relationship between AGE and retinal changes in vivo, we studied the time course of retinopathy over 12 months in trypsin digest preparations and measured glycaemia and retinal AGE in spontaneous diabetic hamsters of mild (MD) and severe (SD) phenotypes. Blood glucose levels were elevated in MD (9.44 ± 0.76 mmol/l) and in SD (3 months: 24.3 ± 1.4 mmol/l; 12 months: 31.7 ± 0.8 mmol/l) over nondiabetic controls (NC: 7.15 ± 0.25 mmol/l; p < 0.05 or less vs MD; p < 0.001 vs SD). Similar relations were found for HbA 1 . Retinal AGE in mild diabetes was 405 ± 11.3 arbitrary units (AU) (NC 245 ± 7.7; p < 0.01) after 3 months and remained unchanged. A non-linear increase of AGE over time was found in severe hyperglycaemic hamsters (466 ± 21 AU after 3 months and 758 ± 21 AU after 12 months; p < 0.001 vs MD). Pericyte loss in mild diabetes progressed from ±26 % after 3 months to ±41 % after 12 months (p < 0.001 vs NC). Whereas the initial pericyte loss in severely diabetic hamsters was identical to the mildly diabetic group, a higher degree of pericyte loss occurred after 12 months (±57 %; p < 0.05 vs MD). Endothelial cell numbers remained unaffected by mild hyperglycaemia, but significantly increased over time in severe diabetes reaching 31.7 % above controls after 12 months (p < 0.001 vs NC and MD). Microaneurysms were absent in all retinae examined. Acellular capillary segments were increased in mild diabetes (3.83 ± 0.31 per mm 2 of retinal area) and severe diabetes (7.83 ± 0.73) over controls (1.0 ± 0.23). These data suggest that a threshold of glycaemia might exist above which AGE removal systems become saturated. Pericyte loss and acellular capillary formation are associated with mild increases in blood glucose and AGE levels while endothelial cell proliferation requires higher glucose and AGE levels. [Diabetologia (1998) 41: 165±170]

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confidence: 99%

The relationship of glycaemic level to advanced glycation end-product (AGE) accumulation and retinal pathology in the spontaneous diabetic hamster

Hammes

Wellensiek

Klöting³

et al. 1998

Diabetologia

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“…Non-diabetic hamsters of both sexes were taken from the M inbred genetic subline. Definitions, metabolic characteristics and genetic background of prediabetic, diabetic and non-diabetic Chinese hamsters have been described in detail elsewhere [29]. Prediabetic and diabetic animals were age-and sex-matched with the nondiabetic animals.…”

Section: Animalsmentioning

confidence: 99%

“…Due to its potent vasodilator activity [24] and its possible involvement in regulation of relaxation [25][26][27] and contraction [28] of the urogenital tract, it was of interest to determine whether concentration and/or distribution of this peptide are altered in the eye and urinary bladder of a suitable diabetic animal model. Since the spontaneously diabetic Chinese hamster is adequately ics, metabolic characteristics and disorders of the eye and urinary bladder [29], it seemed appropriate to evaluate VIP in this species. Therefore, the purpose of the present study was to determine by radioimmunoassay and immunocytochemistry whether VIP was deranged in the eye and urinary bladder of diabetic and prediabetic XA, AC and AH genetic sublines of Chinese hamsters compared with age-matched non-diabetic M subline animals.…”

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

et al. 1985

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Summary. 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.Key words: VIP, radioimmunoassay, immunocytochemistry, eyes, urinary bladder, prediabetes, diabetic Chinese hamsters.Complications of the eye and urinary bladder have been documented in patients with diabetes mellitus and most animal models of this disease. With respect to the eye, lesions have been adequately described in the retina [1][2][3][4][5]. Although the specific type of lesion varies among animals and man, the vasculature of the eye is always adversely affected [5]. Several investigations have demonstrated that distension [6-9] and hypertrophy [10] concomitant with urine retention are characteristic of the urinary bladder of diabetic man and animals. Urinary bladder dysfunction is believed to be a product of diabetic autonomic neuropathy [11,12] which promotes impairment of detrusor muscle function [8,13]. Although it has recently been disputed [9], a reduction in cholinergic innervation [7,14] has been proposed as a possible mechanism which elicits bladder dysfunction. Despite intensive research, the primary aetiological agent(s) underlying the derangements in the eye and urinary bladder of diabetic man and animals remain under investigation.Vasoactive intestinal peptide (VIP) has been shown to be present in high quantities in the eye [15][16][17][18][19] and urogenital tract [20][21][22][23] of several species, including man. Due to its potent vasodilator activity [24] and its possible involvement in regulation of relaxation [25][26][27] and contraction [28] of the urogenital tract, it was of interest to determine whether concentration and/or distribution of this peptide are altered in the eye and urinary bladder of a suitable diabetic animal model. Since the spontaneously diabe...

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“…The overt diabetes range from mild to severe and it is characterized by polyphagia, hyperglycemia, severe polyuria, glucosuria and elevated gluconeogenesis. β-cells present degranulation and hydropic degeneration [63][64][65].…”

Section: Long Evans Tokushima Lean (Letl) a N O U T B R E D C O L O mentioning

confidence: 99%

Development of Improved Animal Models for the Study of Diabetes

Ciobotaru¹

2013

Diabetes Mellitus - Insights and Perspectives

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The Chinese Hamster as a Model for the Study of Diabetes Mellitus

Cited by 61 publications

References 45 publications

The relationship of glycaemic level to advanced glycation end-product (AGE) accumulation and retinal pathology in the spontaneous diabetic hamster

The relationship of glycaemic level to advanced glycation end-product (AGE) accumulation and retinal pathology in the spontaneous diabetic hamster

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

Development of Improved Animal Models for the Study of Diabetes

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