Capillary basement membrane structure: a comparative study of diabetics and sexual ateliotic dwarfs

Merimee, Thomas J.; Siperstein, Marvin D.; Hall, Judith G.; Fineberg, S. Edwin

doi:10.1172/jci106434

Cited by 30 publications

(13 citation statements)

References 15 publications

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“…Studies in ateliotic dwarfs demonstrated a high frequency of diabetes. Despite this, in comparison to matched control patients with type II diabetes, they had a markedly lower frequency of retinopathy and did not have the skeletal muscle capillary basement membranes thickening found in patients with diabetes (41).…”

Section: Discussionmentioning

confidence: 71%

Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro.

Rymaszewski

Cohen

Chomczyński

1991

Proc. Natl. Acad. Sci. U.S.A.

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Growth hormone (GH) has been implicated in the pathogenesis of proliferative diabetic retinopathy. We sought to determine whether this could be mediated by an effect of GH on proliferation of endothelial cells, and, for this purpose, established long-term cultures of human retinal microvascular endothelial cells (hREC) from normal postmortem human eyes. High-purity (>95%) hREC preparations were selected for experiments, based on immunofluorescence with acetylated low density lipoprotein (LDL) and anti-factor VIIIrelated antigen. Growth requirements for these cells were complex, including serum for maintenance at slow growth rates and additional mitogens for more rapid proliferation. Exposure ofhREC to physiologic doses ofhuman GH (hGH) resulted in 100% greater cell number vs. control (P < 0.01) but could be elicited only in the presence of serum. When differing serum conditions were compared, hGH stimulated [3H]thymidine incorporation up to 1.6-to 2.2-fold under each condition and increased DNA content significantly in the presence of human, horse, and fetal calf serum. Depending on the culture conditions used, the threshold hGH concentration for significant stimulation of hREC proliferation was 0.4-4 pg/liter. In contrast, proliferation of human umbilical vein endothelial cells was not significantly altered by hGH added to concentrations as high as 200 pzg/liter. In summary, hREC respond to physiologic concentrations of hGH in vitro with enhanced proliferation. This specific effect of GH on retinal microvascular endothelial cells supports the hypothesis of a role for GH in endothelial cell biology.

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Section: Discussionmentioning

confidence: 71%

Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro.

Rymaszewski

Cohen

Chomczyński

1991

Proc. Natl. Acad. Sci. U.S.A.

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“…On the basis of these and other observations Lundbaek has proposed the provocative theory that somatotropin may be involved in the pathogenesis of diabetic microangiopathy [87]. While the reported beneficial effect of pituitary ablation on diabetic retinopathy [88,89] and reduced skin capillary resistance [90] as well as the apparent absence of microangiopathy in diabetic, somatotropin-deficient dwarfs [91] has supported the "growth hormone hypothesis", no clear biochemical basis for an action of somatotropin on capillary basement membrane synthesis has yet been established. It is known, however, that somatotropin generally stimulates protein synthesis and that diabetic kidney polysomes, contrary to those of liver and muscle, have increased protein synthesizing activity over that of normal [92].…”

Section: Role Of Somatotropinmentioning

confidence: 99%

Search for a biochemical basis of diabetic microangiopathy

1976

Diabetologia

191

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Summary. Diabetic microangiopathy, particularly as seen in the renal glomerulus, is characterized by morphological and biochemical alterations of the capillary basement membrane. Observations from a number of disciplines have indicated that the microvascular disease is not a separately inherited entity but a true consequence or "complication" of insulin deficiency. An evaluation of the biochemical events which could be responsible for the basement membrane lesions of diabetes indicates that the hyperglycemia or plasma somatotropin elevation of this disease alone, or in combination, may play an important role.

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“…It was recently reported that patients with Alströ m syndrome have subtle impairments in the growth hormone-IGF axis with a reduction in acid labile subfraction and IGF binding protein-1, whereas IGF binding protein-2 was shown to be markedly increased (10). These alterations could protect against microvascular complications as in the sex-linked form of ateliotic dwarfism (11,12).…”

Section: Statisticsmentioning

confidence: 99%

Protection From Clinical Peripheral Sensory Neuropathy in Alström Syndrome in Contrast to Early-Onset Type 2 Diabetes

Paisey

Thomson

et al. 2009

Diabetes Care

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OBJECTIVE -Alströ m syndrome, with type 2 diabetes, and blindness could confer a high risk of foot ulceration. Clinical testing for neuropathy in Alströ m syndrome and matched youngonset type 2 diabetic subjects was therefore undertaken.RESEARCH DESIGN AND METHODS -Fifty-eight subjects with Alströ m syndrome (18 insulin-resistant nondiabetic and 40 diabetic; aged 8 -43 years) and 30 young-onset diabetic subjects (aged 13-35 years) were studied. Neuropathy symptom questionnaires were administered. Graded monofilament and 128-MHz tuning fork vibration perception were assessed in both feet.RESULTS -Neuropathic symptoms, loss of monofilament, and/or vibration perception were reported by 12 of the 30 young-onset type 2 diabetic subjects (6 had neuropathic ulceration) but none of the subjects with Alströ m syndrome.CONCLUSIONS -The striking preservation of protective foot sensation in Alströ m syndrome may provide a clue to the causes of differential susceptibility to neuropathy in the wider diabetic population.

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Capillary basement membrane structure: a comparative study of diabetics and sexual ateliotic dwarfs

Cited by 30 publications

References 15 publications

Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro.

Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro.

Search for a biochemical basis of diabetic microangiopathy

Protection From Clinical Peripheral Sensory Neuropathy in Alström Syndrome in Contrast to Early-Onset Type 2 Diabetes

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