Impaired Phagocytic Function and Increased Immune Complexes in Diabetics with Severe Microangiopathy

Iavicoli, M; Mario, U. Di; Pozzilli, Paolo; Canalese, J.; Ventriglia, L; Galfo, C.; Andreani, D

doi:10.2337/diab.31.1.7

Cited by 11 publications

(3 citation statements)

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“…Impairment of the immune system in diabetic subjects is well defined, and its relevance to alteration of phagocytic properties of monocytes/macrophages has also been proposed (22)(23)(24). In the present study, we investigated the involvement of AGE formation in the reduction of phagocytic activity of diabetic macrophages by using flow cytometric analysis with fluorescence-labeled latex particles.…”

Section: Discussionmentioning

confidence: 96%

“…These results suggest the involvement of advanced stages of the Maillard reaction after addition of Amadori product in the phagocytic activity of macrophages. Iavicoli et al (24) reported that the colloid clearance was signific a n t l y reduced in diabetes associated with severe microangiopathy, compared with patients who had no sign of microangiopathy or with normal subjects. They suggested that increased circulating immune complexes in patients with severe microangiopathy may result from an impaired function of fix e d phagocytes.…”

Section: Downregulation Of Phagocytosis Byagesmentioning

confidence: 98%

“…In this regard, diabetes is associated with a dysfunction of the immune system, which enhances the development of infection (21). Several lines of evidence have suggested that impairment of phagocytic function of monocytes/macrophages contributes, at least in part, to the impaired resistance to infection in diabetes (22)(23)(24).…”

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confidence: 99%

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Low phagocytic activity of resident peritoneal macrophages in diabetic mice: relevance to the formation of advanced glycation end products.

et al. 1999

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Formation of advanced glycation end products (AGEs) is accelerated in diabetic subjects along with hyperglycemia. Although several lines of evidence indicate that AGEs stimulate macrophages to secrete several cytokines and growth factors, little is known about the effect of AGEs on the primary function of macrophages, such as phagocytosis. On the other hand, impairment of the phagocytic function of monocytes/macrophages is suggested to contribute to the low resistance to infection in diabetic subjects. In the present study, we examined the effect of AGEs on the phagocytic function of macrophages. Using flow cytometric analysis of mouse resident peritoneal macrophages, we showed that AGEs suppress phagocytosis of fluorescent microspheres by cultured macrophages. In addition, experiments using streptozotocin-induced diabetic mice demonstrated a significant decrease in the phagocytic activity of resident peritoneal macrophages 12 weeks after induction of diabetes compared with age-matched control mice. The phagocytic activity of peritoneal macrophages correlated inversely with AGE content in the adjacent peritoneal tissue. Furthermore, reduced phagocytic activity of macrophages was associated with a reduction in intracellular ATP content. Because phagocytosis is an important component of the defense system, suppression of such activity by AGEs may explain, at least in part, the increased susceptibility of diabetic patients to infection.

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Section: Discussionmentioning

confidence: 96%

Section: Downregulation Of Phagocytosis Byagesmentioning

confidence: 98%

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Low phagocytic activity of resident peritoneal macrophages in diabetic mice: relevance to the formation of advanced glycation end products.

et al. 1999

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Complications of Insulin Therapy

Fineberg

Anderson

2003

International Textbook of Diabetes Mellitus

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Insulin allergic reactions were seen in the first insulin preparations used for therapy of diabetes mellitus. The use of highly purified animal insulins, semisynthetic, and recombinant DNA human insulins has resulted in a dramatic reduction in the immunological complications of insulin therapy. However, subcutaneous human insulin administration with biosynthetic insulins has been shown to incite antibody responses in nondiabetic individuals as well as in diabetic individuals via subcutaneous, respiratory, and peritoneal routes. Further, anti‐insulin antibodies commonly precede the appearance of type 1 diabetes, especially in children. Hypertrophy of subcutaneous fat at sites of repeated insulin injections continues to be a common nonimmunological complication of therapy. In addition, hypertrophy of omental fat has been reported to be a cause of catheter occlusion during the course of intraperitoneal delivery of concentrated insulin by implantable insulin pumps. Edema associated with insulin therapy is an unusual and usually self‐limited disorder. Hypoglycemia secondary to insulin therapy is the expected outcome of a mismatch between nutrients, insulin levels, insulin action, and glucose counterregulatory mechanisms. This chapter reviews insulin immunology and the immunological and nonimmunological complications of insulin therapy.

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Antibodies to human albumin epitopes in Type 1 (insulin-dependent) diabetes mellitus

1988

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The presence of antibodies to glycosylated albumin was studied by means of a newly developed sandwich enzyme-linked immunosorbent assay in 29 long-standing Type 1 (insulin-dependent) diabetic patients with microvascular complications and in 20 normal subjects. Two types of antibody reactivity were detected. One directed against glucitol-albumin expressing G and M isotypes. The second, predominantly belonging to the IgG class, reacted with an epitope shared by non-glycosylated albumin and the ketoamine adduct of albumin glycosylation. Both types of antibodies, with affinity constant ranging from 10(4) to 10(7) (mol/l)-1 were found in normal and diabetic subjects, but higher titres were significantly more prevalent in the diabetic patients. These antibodies may represent the result of immune tolerance breakdown or, alternatively, be natural antibodies. Although their function remains to be established, their raised prevalence in Type 1 diabetes may be relevant to diabetic microvascular disease.

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Impaired Phagocytic Function and Increased Immune Complexes in Diabetics with Severe Microangiopathy

Cited by 11 publications

References 2 publications

Low phagocytic activity of resident peritoneal macrophages in diabetic mice: relevance to the formation of advanced glycation end products.

Low phagocytic activity of resident peritoneal macrophages in diabetic mice: relevance to the formation of advanced glycation end products.

Complications of Insulin Therapy

Antibodies to human albumin epitopes in Type 1 (insulin-dependent) diabetes mellitus

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