Infusion of synthetic human C-peptide does not affect plasma glucose, serum insulin, or plasma glucagon in healthy subjects.

We studied six healthy male subjects to determine whether a four-hour infusion of synthetic human C-peptide sufficient to achieve mean (+/- SD) peripheral plasma concentrations of 1.3 +/- 0.7 pmol/mL affected plasma glucose, serum insulin, or plasma glucagon. Subjects were studied in a fasting state and following an oral glucose load during four-hour 0.9% NaCl (control) and C-peptide (mean dose: 70 nmol) infusions. No differences were observed between saline and C-peptide infusions for mean values of fasting plasma glucose (94 +/- 6 v 87 +/- 5 mg/dL), serum insulin (3 +/- 1 v 2 +/- 1 microU/mL), or plasma glucagon (124 +/- 65 v 112 +/- 70 pg/dL). Following oral glucose ingestion no differences were detected between saline and C-peptide infusions for mean peak values of plasma glucose (168 +/- 18 v 168 +/- 31) and serum insulin (59 +/- 6 v 57 +/- 21) or mean nadir values of plasma glucagon (80 +/- 73 v 75 +/- 70). There was a slight delay in the insulin rise following oral glucose on the C-peptide infusion day, but differences between mean values for individual sampling times were not statistically significantly different.

Hormonal and metabolic effects of a pancreatic endocrine graft. Vascularized segmental transplantation in insulin-dependent diabetic patients.

A new modification of pancreas transplant technique, the vascularized segmental intraperitoneal graft without duct ligation, has provided reversal of insulin-dependent (type I) diabetes mellitus for as long as 2 years of comfortable life. Although the risks associated with immunosuppression remain high (two of the 12 patients have died of early postoperative infection), selected data are presented from six cases to show the following striking hormonal and metabolic results after transplantation and withdrawal of insulin: restoration of normal beta cell function as shown by 24-hour urine C-peptide excretion and acutely responsive serum insulin, restoration of normal suppressibility of plasma glucagon, elimination of ketosis and negative nitrogen balance, normal fasting plasma glucose and glycosylated hemoglobin, and normal or near-normal glucose tolerance. These results provide a standard for current explorations of new ways of treating insulin-dependent diabetes.

Lack of glucagon response to hypoglycemia in diabetic autonomic neuropathy.

Glucagon response to insulin hypoglycemia was tested in diabetics with autonomic neuropathy (N=9), diabetics without neuropathy (N=8), and normals (N=9). With similar levels of hypoglycemia, growth hormone and plasma cortisol increased in all groups. The glucagon response in normals (121+/-19 vs. 308+/-30 pg./ml., mean+/-S.E.M. of baseline vs. hypoglycemia peak) was significantly less in nonneuropathic diabetics than in normals (128+/-13 vs. 209+/-30) and absent in neuropathic diabetes (128+/-23 vs. 115+/-20). Arginine stimulation produced a glucagon response in the neuropathic diabetics (106+/-16 vs. 523+/-103). The data indicate that the capacity to release glucagon during hypoglycemia is lost in diabetic neuropathy while glucagon responsiveness to arginine is retained. Neuropathy in diabetes may contribute to metabolic instability.

Xylitol, a partial homologue ot alpha-D-glucopyranose: potent stimulator of insulin release in dogs.

A direct comparison was made in healthy female dogs of the potency of xylitol and mutarotated glucose as stimulators of insulin release (both first and second phases), and also of their urinary excretion and arterio-venous difference across a hind-limb. Xylitol or glucose was given by constant infusion into a systemic vein for 50 minutes in paired experiments. Three dose levels were used in 12 dogs. Plasma insulin levels during xylitol infusion were as high as or higher than those during glucose infusion, with increases in arterial xylitol levels equal to or less than those in glucose. More xylitol was lost in the urine, but the overall uptake of xylitol was at least 70% also the arteriovenous difference for xylitol across the hind-limb was greater than for glucose, when each was divided by the arterial sugar concentration. It is suggested that both the striking potency of xylitol in stimulating both phases of insulin release, and its rapid uptake by tissues, may result from its homology with alpha-D-glucopyranose, the alpha-anomer of glucose. The concept of a glucoreceptor on the surface of the pancreatic beta-cell, with stereospecificity for alpha-D-glucopyranose or closely similar molecules, is supported by our results.