The Metabolic Effects of Biosynthetic Human Proinsulin in Individuals with Type I Diabetes*

Bergenstal, Richard M.; Cohen, Robert M.; Lever, Eric G.; Polonsky, Kenneth S.; Jaspan, J. B.; Blix, Petra M.; Revers, Robert R.; Olefsky, Jerrold M.; Kolterman, Orville G.; Steiner, Kurt; Cherrington, Alan D.; Frank, Bruce H.; Galloway, John A.; Rubenstein, Arthur H.

doi:10.1210/jcem-58-6-973

Cited by 48 publications

(24 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is no evidence of a changed metabolic clearance rate of either proinsulin or C-peptide in diabetic subjects [21][22][23]. Thus, apart from the possible modulating effect of insulin, it seems justified that the plateau-shaped further elevation of proinsutin/C-peptide ratio in the placebo group reflects alterations of B-cell function during remission and relapse.…”

Section: Discussionmentioning

confidence: 95%

Proinsulin and C-peptide at onset and during 12 months cyclosporin treatment of Type 1 (insulin-dependent) diabetes mellitus

Snorgaard¹,

Hartling²,

Binder³

1990

Diabetologia

View full text Add to dashboard Cite

Smnmary. An increased proinsulin to C-peptide molar ratio at the onset of Type i (insulin-dependent) diabetes mellitus has been suggested. We studied fasting proinsulin levels and proinsulin/C-peptide ratios in the newly diagnosed diabetic subjects participating in the Canadian/European placebo controlled cyclosporin study at entry, during the one year treatment period and six months of follow-up. Available entry data from 176 out of the 188 allocated patients were compared to 60 age and weight matched control subjects. Fasting proinsulin was significantly elevated in male patients compared to male control subjects (p < 0.01), whereas the levels only tended to be elevated in female patients. The proinsulin/C-peptide ratio was three to fourfold elevated in the diabetic groups of both sexes, (p < 0.001). Further, proinsulin and C-peptide were studied in 83 cyclosporin and 86 placebo-treated subjects during the trial and follow-up. An additional increase of proinsulin/C-peptide ratio was observed during the first three months of placebo treatment. It remained constantly high for nine months and then declined to entry level. This pattern was not seen in the cyclosporintreated group, where the ratio was unchanged during the 12 months trial and follow-up. The effect of cyclosporin on the induction of non-insulin requiring remission was unrelated to fasting and glucagon stimulated C-peptide levels at entry, whereas 64% of the cyclosporin-treated against 28% of the placebo-treated subjects (p < 0.01) went into remission if the proinsulin/C-peptide ratio at entry was above 0.024. If the ratio was below 0.024 at entry, 42% and 33% went into noninsulin requiring remission, respectively (NS). We conclude that fasting proinsulin to C-peptide molar ratio is elevated at the onset of Type i diabetes mellitus. A further plateaushape elevation lasting nine months was seen during the remission period. Cyclosporin seems to inhibit or delay this development. The proinsulin/C-peptide ratio at diagnosis may show to be of value in the prediction of remission during cyclosporin treatment.

show abstract

Section: Discussionmentioning

confidence: 95%

Proinsulin and C-peptide at onset and during 12 months cyclosporin treatment of Type 1 (insulin-dependent) diabetes mellitus

Snorgaard¹,

Hartling²,

Binder³

1990

Diabetologia

View full text Add to dashboard Cite

show abstract

“…The proinsulin clearance rate in Type 2 diabetic patients has never been studied, but it is unlikely that it is much affected by the diabetic state because the half-life of exogenously administered proinsulin was reported to be similar in both healthy subjects and Type 1 diabetic patients [16]. Assuming that diabetic Beta cells secrete proinsulin at a larger amount relative to insulin, there would be still several different possibilities.…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinaemia in obesity is not accompanied by an increase in serum proinsulin/insulin ratio in groups of human subjects with and without glucose intolerance

et al. 1991

View full text Add to dashboard Cite

Summary. Serum proinsulin is disproportionately elevated compared to insulin in Type2 (non-insulin-dependent) diabetes mellitus. We studied the effect of obesity on serum proinsulin with varying degrees of glucose intolerance. Serum proinsulin and insulin were measured during a 75 g oral glucose tolerance test in 73 obese and 74 non-obese subjects with normal, borderline or diabetic-type glucose tolerance. Proinsulin was assayed by a direct radioimmunoassay using proinsulin-specific antiserum. Fasting serum proinsulin and insulin and the summed values of proinsulin and insulin during oral glucose tolerance test were significantly, or tended to be, higher in obese subjects than in those without obesity in each category of glucose tolerance. However, the molar ratio of proinsulin to insulin was nearly the same between obese and non-obese groups with a similar degree of glucose tolerance. On the other hand, the proinsulin/insulin ratio increased progressively with the deterioration of glucose tolerance. We conclude that proinsulin secretion is disproportionately increased in the presence of glucose intolerance but not by obesity itself. Each Beta cell seems to function normally in obese subjects while glucose tolerance remains normal.

show abstract

“…ratio in the blood is that relative metabolic clearance rates of proinsulin and insulin by the liver and other tissues are altered in the diabetic state. This has not been studied in detail, although there are reports which show that the metabolic clearance rate of proinsulin is about onethird or one-fifth that of insulin in healthy subjects and in patients with Type 1 (insulin-dependent) diabetes [20].…”

Section: Discussionmentioning

confidence: 99%

Serum proinsulin levels at fasting and after oral glucose load in patients with Type 2 (non-insulin-dependent) diabetes mellitus

et al. 1988

View full text Add to dashboard Cite

A simple and sensitive human proinsulin radioimmunoassay system was developed using guinea pig anti-proinsulin serum, which cross-reacted neither with human insulin nor C-peptide. The recognition site of the antiserum seems to be located near the junction between the B chain and C-peptide. With this assay system, we studied the serum proinsulin concentration at fasting and after an oral 100 g glucose load in 25 healthy subjects, 21 subjects with impaired glucose tolerance and 40 patients with Type 2 (non-insulin-dependent) diabetes mellitus. At fasting, serum proinsulin was 5.8 +/- 3.3 pmol/l in normal subjects as compared to 9.5 +/- 6.9 pmol/l (p less than 0.05) in subjects with impaired glucose tolerance and 12.6 +/- 7.5 pmol/l (p less than 0.001) in diabetic patients. The molar ratio of proinsulin to insulin was also increased in subjects with impaired glucose tolerance or diabetes compared to control subjects. After a 100 g oral glucose load, serum proinsulin increased more slowly than insulin. The proinsulin response after an oral glucose load was augmented in subjects with impaired glucose tolerance and diabetes, while the insulin response decreased with the elevation of fasting plasma glucose. Diabetic patients with high fasting plasma glucose had a very poor insulin response, but the proinsulin response was similar to control subjects. There was a linear correlation between summed proinsulin values and summed insulin values, but the slope of the regression line was steeper in diabetic patients than in control subjects. There was a relative increase in serum proinsulin both in subjects with impaired glucose tolerance and diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

The Metabolic Effects of Biosynthetic Human Proinsulin in Individuals with Type I Diabetes*

Cited by 48 publications

References 19 publications

Proinsulin and C-peptide at onset and during 12 months cyclosporin treatment of Type 1 (insulin-dependent) diabetes mellitus

Proinsulin and C-peptide at onset and during 12 months cyclosporin treatment of Type 1 (insulin-dependent) diabetes mellitus

Hyperinsulinaemia in obesity is not accompanied by an increase in serum proinsulin/insulin ratio in groups of human subjects with and without glucose intolerance

Serum proinsulin levels at fasting and after oral glucose load in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Contact Info

Product

Resources

About