{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T04:27:49Z","timestamp":1765600069925,"version":"3.48.0"},"reference-count":14,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"published-print":{"date-parts":[[1994,11]]},"abstract":"<jats:p>AIMS--To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism. METHODS--Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five day periods; (2) acute changes in calcium concentration in eight subjects who received 25 mmol oral calcium; (3) chronic changes in calcium concentration in seven patients with primary hyperparathyroidism and five with pseudohypoparathyroidism. RESULTS--Acid base changes were confirmed by rises in serum bicarbonate concentrations (p &lt; 0.01). No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol\/l; p &lt; 0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol\/l; p &lt; 0.01) two hours after acute calcium loading. There were no significant differences in serum glucose, insulin, or intact proinsulin concentrations. Fasting proinsulin concentrations were significantly lower in the hyperparathyroid group (1.1 v 2.1 pmol\/l; p &lt; 0.05) and increased significantly after parathyroidectomy (2.1 v 1.1 pmol\/l; p &lt; 0.05). CONCLUSIONS--The results indicate that subacute acid base changes do not affect proinsulin cleavage. Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia may influence the mechanism of insulin secretion.<\/jats:p>","DOI":"10.1136\/jcp.47.11.982","type":"journal-article","created":{"date-parts":[[2007,6,9]],"date-time":"2007-06-09T00:50:46Z","timestamp":1181350246000},"page":"982-985","source":"Crossref","is-referenced-by-count":2,"title":["Effects of changes in acid base and calcium concentration on fasting serum insulin, proinsulin, and glucose concentrations."],"prefix":"10.1136","volume":"47","author":[{"given":"W S","family":"Smellie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"O'Donnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Couper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F C","family":"Logue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1994,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/333093a0","article-title":"Intraorganellar Ca and pH control proinsulin cleavage in the pancreatic B-cell via two distinct site-specific endopeptidases","volume":"333","author":"Davidson, H.W.; Rhodes, C.J.; Hutton, J.C.","year":"1988","unstructured":"Davidson HW, Rhodes CJ, Hutton JC. Intraorganellar Ca and pH control proinsulin cleavage in the pancreatic B-cell via two distinct site-specific endopeptidases. Nature 1988;333:93-6.","journal-title":"Nature"},{"key":"ref_2","first-page":"1396","article-title":"Biochemical and clinical implications of proinsulin conversion intermediates","volume":"76","author":"Given, B.D.; Cohen, R.M.; Shoelson, S.E.; Frank, B.H.; Rubenstein, A.H.; Tager, H.S.","year":"1985","unstructured":"Given BD, Cohen RM, Shoelson SE, Frank BH, Rubenstein AH, Tager HS. Biochemical and clinical implications of proinsulin conversion intermediates. J Clin Invest 1985;76:1396-405.","journal-title":"J Clin Invest"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1042\/bj2450575","article-title":"The insulin-secretory-glanule carboxypeptidase H. Purification and demonstration of involvement in proinsulin processing","volume":"7","author":"Davidson, H.W.; Hutton, J.C.","year":"1987","unstructured":"Davidson HW, Hutton JC. The insulin-secretory-glanule carboxypeptidase H. Purification and demonstration of involvement in proinsulin processing. Biochem J7 1987; 245:575-82.","journal-title":"Biochem"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1042\/bj2600535","article-title":"Sensitive and specific two-site immunoradiometric assays for insulin proinsulin 65-66 and 32-33 split proinsulin","volume":"260","author":"Sobey, W.J.; Beer, S.F.; Carrington, C.A.; Clark, P.M.S.; Frank, B.H.; Gray, I.P.","year":"1989","unstructured":"Sobey WJ, Beer SF, Carrington CA, Clark PMS, Frank BH, Gray IP, et al. Sensitive and specific two-site immunoradiometric assays for insulin proinsulin 65-66 and 32-33 split proinsulin. Biochem Jf 1989;260:535-41.","journal-title":"Biochem Jf"},{"key":"ref_5","first-page":"845","article-title":"The effect of insulin on renal handling of sodium, potassium, calcium and phosphate in man. J7 Clin Invest","volume":"55","author":"RA, De Fronzo; CR, Cooke; R, Andres; GR, Faloona; PJ, Davis","year":"1975","unstructured":"De Fronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal handling of sodium, potassium, calcium and phosphate in man. J7 Clin Invest 1975;55:845-55."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1210\/jcem-53-6-1154","article-title":"Alterations in circulating vitamin D metabolites in the young insulin-dependent diabetic","volume":"53","author":"Frazer, T.E.; White, N.H.; Hough, S.; Santiago, J.V.; McGee, B.R.; Bryce, G.","year":"1981","unstructured":"Frazer TE, White NH, Hough S, Santiago JV, McGee BR, Bryce G, et al. Alterations in circulating vitamin D metabolites in the young insulin-dependent diabetic. Jf Clin Endocrinol Metab 1981;53:1154-9.","journal-title":"Jf Clin Endocrinol Metab"},{"key":"ref_7","first-page":"209","article-title":"The influence of glucose and insulin on calcium excretion in the urine","volume-title":"related clinical research","author":"Willis, R.G.; Green, R.; Gordon, C.","year":"1985","unstructured":"Willis RG, Green R, Gordon C. The influence of glucose and insulin on calcium excretion in the urine. In: Schwille PO, Smith LH, Robertson WG, et al, eds. Urolithiasis and related clinical research. New York: Plenum Press, 1985:209-12."},{"key":"ref_8","first-page":"293","article-title":"Insulin deficiency in non insulin-dependent diabetes","volume":"i:","author":"Temple, R.C.; Carrington, C.A.; Luzio, S.D.; Owens, D.R.; Schneider, A.E.; Sobey, W.J.","year":"1989","unstructured":"Temple RC, Carrington CA, Luzio SD, Owens DR, Schneider AE, Sobey WJ, et al. Insulin deficiency in non insulin-dependent diabetes. Lancet 1989;i:293-5.","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/230581a0","article-title":"Calcium shift into bone causing transient hypocalcaemia after injection of parathyroid hormone","volume":"230","author":"Parsons, J.A.; Robinson, C.J.","year":"1971","unstructured":"Parsons JA, Robinson CJ. Calcium shift into bone causing transient hypocalcaemia after injection of parathyroid hormone. Nature 1971;230:581-2.","journal-title":"Nature"},{"issue":"48","key":"ref_10","first-page":"1832","article-title":"Pseudohypoparathyroid: Defective excretion of 3'5'-AMP in response to parathyroid hormone","volume":"1969","author":"Chase, L.R.; Melson, G.L.; Aurbach, G.D.","unstructured":"Chase LR, Melson GL, Aurbach GD. Pseudohypoparathyroid: Defective excretion of 3'5'-AMP in response to parathyroid hormone. Jf Clin Invest 1969; 48:1832-44.","journal-title":"Jf Clin Invest"},{"key":"ref_11","first-page":"15","article-title":"A comparison of inter-individual variability of fasting serum intact proinsulin and insulin concentrations","volume":"5","author":"Smellie, W.S.A.; McConway, M.; O'Donnell, J.G.; Couper, J.; St, O.'Reilly D.; J.","year":"1993","unstructured":"Smellie WSA, McConway M, O'Donnell JG, Couper J, O'Reilly D St J. A comparison of inter-individual variability of fasting serum intact proinsulin and insulin concentrations. Communications in Laboratory Medicine 1993;5: 15-20.","journal-title":"Communications in Laboratory Medicine"},{"key":"ref_12","first-page":"\"using\" # \"160","article-title":"A two-site immunomeric assay for PTH","volume":"28","author":"Logue, F.C.; Perry, B.; Chapman, R.S.; Mine, I.; James, K.; Beastall, G.H.","year":"1991","unstructured":"Logue FC, Perry B, Chapman RS, Mine I, James K, Beastall GH. A two-site immunomeric assay for PTH (1-84) using N and C terminal specific monoclonal antibodies. Ann Clin Biochem 1991;28:160-6.","journal-title":"Ann Clin Biochem"},{"key":"ref_13","first-page":"2","article-title":"Pathogenesis of glucose intolerance in uraemia","volume":"27","author":"RA, De Fronzo","year":"1979","unstructured":"De Fronzo RA. Pathogenesis of glucose intolerance in uraemia. Metabolism 1979;27(Suppl 2):1866-80.","journal-title":"Metabolism"},{"key":"ref_14","first-page":"10","article-title":"Hyperinsulinism of hepatic cirrhosis: diminished degradation or hypersecretion","volume":"i:","author":"Johnston, D.G.; Alberti, K.G.M.M.; Faber, O.K.; Binder, C.; Wright, R.","year":"1977","unstructured":"Johnston DG, Alberti KGMM, Faber OK, Binder C, Wright R. Hyperinsulinism of hepatic cirrhosis: diminished degradation or hypersecretion. 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