Sulfated Insulin for Treatment of Insulin‐Resistant Diabetics

Moloney, P. J.; Aprile, M; Wilson, S.

doi:10.1002/j.1552-4604.1964.tb00356.x

Cited by 42 publications

(18 citation statements)

References 10 publications

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“…Certain of these modifications are situated in regions of the A-and B-chain that we have shown contribute to the formation of three immunodominant conformational epitopes of insulin recognized by human T cells (9). SBI is much less immunogenic both in vivo (23)(24)(25) and in vitro (this report) than either BI or PI. Addition of many negatively charged groups to insulin may alter its tertiary conformation, kinetics, and pathway of processing by an APC, or the capacity of a processed fragment(s) either to bind to HLA-D region encoded class II antigens or to be recognized with sufficient avidity by helper T cell antigen receptors.…”

Section: Discussionmentioning

confidence: 65%

“…Sulfation of insulin adds sulfate groups (average of six out of a possible eight per molecule) to side chains of threonine, serine, and tyrosine residues (23,24). Certain of these modifications are situated in regions of the A-and B-chain that we have shown contribute to the formation of three immunodominant conformational epitopes of insulin recognized by human T cells (9).…”

Section: Discussionmentioning

confidence: 83%

“…SBI is currently manufactured by treatment of BI with H2SO4 for 20 min at room temperature (23,27). When SBI is chromatographed by HPLC on a reverse-phase C18 column using various buffer systems, several poorly resolved peaks are observed (Naquet, P., unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

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Sulfated beef insulin treatment elicits CD8+ T cells that may abrogate immunologic insulin resistance in type I diabetes.

Naquet¹,

Ellis²,

Kenshole³

et al. 1989

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 83%

See 1 more Smart Citation

Sulfated beef insulin treatment elicits CD8+ T cells that may abrogate immunologic insulin resistance in type I diabetes.

Naquet¹,

Ellis²,

Kenshole³

et al. 1989

J. Clin. Invest.

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“…Obviously, hypoglycemia is essential for the stimulation of glucagon secretion, since maintenance ofeuglycemia despite increased removal of glucose associated with hyperinsulinemia was reported not to increase glucagon secretion (33). This was confirmed in the euglycemic clamp studies (data not shown).…”

Section: Discussionmentioning

confidence: 52%

Effect of metabolic clearance rate and hepatic extraction of insulin on hepatic and peripheral contributions to hypoglycemia.

Chap¹,

Ishida²,

Chou³

et al. 1985

J. Clin. Invest.

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The liver is a major site of uptake, degradation, and biologic action of insulin. It is not known, however, whether all of the hormone extracted by that organ exerts a biological effect or whether extraction may be independent of any physiological action. In addition, the rate of hepatic extraction affects peripheral levels of the hormone. The effects of insulin on glucose utilization (peripheral effect) and suppression of glucose production (hepatic effect) are dose-related processes with different sensitivities and insulin saturating levels (1). On this basis we evaluated the effects ofdifferences in fractional hepatic extraction of insulin with its resulting change in the concentrations and relative distribution of the hormone between the portal vein (predominantly hepatic effect) and arterial (peripheral effect) blood compartments. Such alterations may produce different contributions by the liver and peripheral tissues to the ensuing hypoglycemia. Since hypoglycemia triggers counterregulatory hormone secretion, which increases glucose production (2-7), this may modify the effect of insulin on hepatic glucose production. To examine these questions we compared insulin and sulfated insulin, which has markedly lower hepatic extraction, on the mechanism of hypoglycemia. This involved measurements of their effects on glucose levels, appearance, disappearance, and clearance, and the counterregulatory responses ofglucagon. Their binding to liver plasma membranes and these various interrelationships were also examined.Our data indicate that the significantly lower hepatic extraction of sulfated insulin caused higher concentrations of the hormone and significantly different relative distribution between the portal vein and arterial blood compartments. This results in significantly different contributions by the liver and peripheral tissues to the same hypoglycemia and was associated with greater counterregulatory effect on glucose production. Methods Materials

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“…Patients 1-18 were 54 IBI, insulin binding index; IBI <60 considered indicative of significant insulin binding. 48 IAI, insulin antibody index in /nU/ml; norms according to duration of insulin treatment. 5 included in the review of insulin resistance in children by Guthrie et al in 1967.…”

Section: Case Reportsmentioning

confidence: 99%

Insulin Resistance Developing in Children with IDDM

Cuttler

Ehrlich

1982

Diabetes Care

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In a review of the 1000 children with insulin-dependent diabetes mellitus (IDDM) followed at The Hospital for Sick Children, Toronto, between 1970 and 1980, insulin resistance (IR) was noted in 3 after initial sensitivity to exogenous insulin. One was an otherwise typical patient with IDDM. One had cystic fibrosis and is the first such patient with IR to be reported. These two had high insulin antibody titers and responded dramatically to sulfated insulin. The third patient had hyperthyroidism. Although she also had a high anti-insulin antibody titer, IR was controlled only when she was given propylthiouracil. She is the first reported child with IR and hyperthyroidism. The literature on IR in children with IDDM is reviewed. With our 3 patients included, a total of 29 children have been reported. Their mean age is 12.9 yr, 72% are female, and 41% had associated illnesses. Insulin antibodies were elevated in 71% of those in whom measurement was attempted. Of those whose outcome is reported, 67% improved, 21% continued to have IR, and 12% died.

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Sulfated Insulin for Treatment of Insulin‐Resistant Diabetics

Cited by 42 publications

References 10 publications

Sulfated beef insulin treatment elicits CD8+ T cells that may abrogate immunologic insulin resistance in type I diabetes.

Sulfated beef insulin treatment elicits CD8+ T cells that may abrogate immunologic insulin resistance in type I diabetes.

Effect of metabolic clearance rate and hepatic extraction of insulin on hepatic and peripheral contributions to hypoglycemia.

Insulin Resistance Developing in Children with IDDM

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