Diabetes-like vascular lesions in the kidneys of guinea pigs immunized with an insulin-adjuvant mixture

Andreev, D; Ditzov, Stefan; Dashev, G

doi:10.1007/bf01556785

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…Although there is a general consensus that IC circulate in the sera of diabetic patients (10)(11)(12)(20)(21)(22)(23), little is known about their specific nature. Studies performed in this laboratory previously showed that insulin-antiinsulinsoluble IC form in a large proportion of patients treated with heterologous insulins (24,25).…”

Section: Discussionmentioning

confidence: 99%

“…Among these factors, IC are believed to play a role in the pathogenesis of diabetic macro-and microangiopathy. Several facts seem to support this hypothesis: Vascular lesions present in people with immune complex disease share morphological characteristics with those observed in people with diabetes (5-7), diabetic-like vascular lesions can be experimentally induced by immune mechanisms (8)(9)(10), and circulating IC were described in diabetic subjects (11,12). Recently, it was shown that modification of lipoproteins, such as glycation and oxidation, renders lipoproteins immunogenic (13,14) and triggers antibody and immune-complex formation.…”

mentioning

confidence: 96%

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Lipoprotein-lmmune Complexes and Diabetic Vascular Complications

Gisinger

Lopes‐Virella²

1992

Diabetes

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In earlier studies, we showed that incubation of HMM with LDL IC led to cellular CE accumulation and to the transformation of macrophages into foam cells. This study demonstrates that the stimulation of macrophages with RBC-LDL-IC also increases the uptake of native LDL, most likely because of an increased LDL receptor number, as shown by Scatchard plot analysis (x-axis intercept 1267 vs. 352 ng LDL/mg protein in control cells). To determine whether the increase in LDL-receptor activity was secondary to a decrease in the macrophage free (nonassociated) cholesterol content, we measured the T-UC and the UC associated with intracellular intact LDL and demonstrated that 50% of the T-UC is associated with intact LDL. UC not associated with LDL (free cholesterol) was lower in LDL-IC-stimulated cells than in control cells. These results suggest that UC associated with nondegraded intracellular LDL is nonregulatory, a conclusion that was also supported by finding increased sterol synthesis (192.8 +/- 22.9 pmol/mg protein vs. 94.8 +/- 11.8) in RBC-LDL-IC-stimulated macrophages. In conclusion, the uptake of RBC-LDL-IC by macrophages led to increased intracellular accumulation of CE and UC, to a decrease in the cell regulatory pool of free cholesterol, and to an increase in LDL-receptor activity.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

Lipoprotein-lmmune Complexes and Diabetic Vascular Complications

Gisinger

Lopes‐Virella²

1992

Diabetes

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“…A series of reports published from the 1960s through the 1980s yielded conflicting results regarding insulin-antiinsulin immune complexes in the development of long-term diabetic complications in animal models (319). Studies in humans have not shown consistent links between IAs and diabetic complications.…”

Section: F Immune Complexesmentioning

confidence: 98%

Immunological Responses to Exogenous Insulin

et al. 2007

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Regardless of purity and origin, therapeutic insulins continue to be immunogenic in humans. However, severe immunological complications occur rarely, and less severe events affect a small minority of patients. Insulin autoantibodies (IAAs) may be detectable in insulin-naive individuals who have a high likelihood of developing type 1 diabetes or in patients who have had viral disorders, have been treated with various drugs, or have autoimmune disorders or paraneoplastic syndromes. This suggests that under certain circumstances, immune tolerance to insulin can be overcome. Factors that can lead to more or less susceptibility to humoral responses to exogenous insulin include the recipient's immune response genes, age, the presence of sufficient circulating autologous insulin, and the site of insulin delivery. Little proof exists, however, that the development of insulin antibodies (IAs) to exogenous insulin therapy affects integrated glucose control, insulin dose requirements, and incidence of hypoglycemia, or contributes to beta-cell failure or to long-term complications of diabetes. Studies in which pregnant women with diabetes were monitored for glycemic control argue against a connection between IAs and fetal risk. Although studies have shown increased levels of immune complexes in patients with diabetic microangiopathic complications, these immune complexes often do not contain insulin or IAs, and insulin administration does not contribute to their formation. The majority of studies have shown no relationship between IAs and diabetic angiopathic complications, including nephropathy, retinopathy, and neuropathy. With the advent of novel insulin formulations and delivery systems, such as insulin pumps and inhaled insulin, examination of these issues is increasingly relevant.

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“…Whilst various processes have been shown to be involved in diabetic microvascular lesions, certain findings appear to be of particular interest: vascular lesions present in immune complex diseases share morphological aspects with those observed in diabetes (Blumen¬ thal et al. 1964;Bloodworth 1968;Andreani et al 1971), diabetic like vascular lesions can be experi¬ mentally induced by immune mechanisms (Mohos et al 1963; Zampa & Mancini 1965;Andreev et al 1970), circulating immune complexes have been described in diabetics (Irvine et al 1977;Kumar & Quismorio 1978;Ludwigetal. 1978;Delespesse et al 1980) mainly in those with retinopathy (Irvine et al 1978b;Bodanskyetal.…”

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confidence: 99%

Circulating immune complexes in diabetics with severe microangiopathy: evaluation by two different methods

Andreani¹,

Mario²,

Galfo³

et al. 1982

Acta Endocrinologica

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Abstract. An investigation on circulating immune complexes (AgAb) was carried out in 80 diabetics with severe microangiopathy and in 71 diabetics without microvascular lesions. The duration of the disease, the type of diabetes, the type of treatment and the main localization of microangiopathy (retinopathy and nephropathy) were taken into account. AgAb were detected by two different methods: the solid phase Clq binding test (ClqSP) and the conglutinin binding test (KgBt). AgAb detected by ClqSP were increased both in prevalence and quantities in diabetics with severe microangiopathy regardless of the duration of the disease and the type of diabetes. Long standing diabetics without microangiopathy had similar prevalence of AgAb as normal controls. The presence of AgAb was not in correlation with the type of treatment and was similar in diabetics with retinopathy and in those with nephropathy. When AgAb were detected by KgBt, they were found with higher prevalence in diabetics than in normal controls but no correlation with microangiopathy was observed. AgAb, detected by KgBt, were higher in long standing type I diabetics. Since the two methods detect different AgAb it is concluded that AgAb present in diabetics seem to be heterogenous and part of them are related to the presence of microangiopathy.

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Diabetes-like vascular lesions in the kidneys of guinea pigs immunized with an insulin-adjuvant mixture

Cited by 8 publications

References 11 publications

Lipoprotein-lmmune Complexes and Diabetic Vascular Complications

Lipoprotein-lmmune Complexes and Diabetic Vascular Complications

Immunological Responses to Exogenous Insulin

Circulating immune complexes in diabetics with severe microangiopathy: evaluation by two different methods

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