Detail of "11061-68-0"

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Suppression of basal, but not of glucose-stimulated, insulin secretion by human insulin in healthy and obese hyperinsulinemic subjects

Suppression of basal, but not of glucose-stimulated, insulin secretion by human insulin in healthy and obese hyperinsulinemic subjects. Bratusch-Marrain, Paul R.; Waldhaeusl, Werner K. (Div. Clin. Endocrinol. Diabes Mellitus, I. Med. Universitaetsklin. Wien, Vienna, Austria). Metab., Clin. Exp., 34(2), 188-93 (English) 1985. CODEN: METAAJ. ISSN: 0026-0495. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) To evaluate the suppressive effect of biosynthetic human insulin (BHI) [11061-68-0] (2.5 units/m2/h) on basal and glucose [50-99-7]-stimulated insulin [9004-10-8] secretion in healthy and obese hyperinsulinemic subjects, the plasma proinsulin C-peptide [59112-80-0] response was measured during maintenance of euglycemia and hyperglycemia by means of the glucose clamp technique. In healthy subjects in whom arterial insulin concn. was increased to 94 microunits/mL, but euglycemia was maintained at the fasting level, C-peptide concn. fell from 1.3 ng/mL by 21%. When hyperglycemia of 7 mmol/L above basal was induced by a variable glucose infusion, the C-peptide response was similar in the control and BHI expts. and was paralleled by an identical increase in plasma insulin above the prevailing insulin concn. In obese patients plasma C-peptide fell from 3.5 to 2.8 ng/mL when BHI was infused at the same rate and euglycemia was maintained as in the lean subjects. As in healthy subjects, however, the plasma C-peptide response to the hyperglycemic stimulus was not altered by BHI. Glucose utilization as detd. by the glucose infusion rate necessary to maintain the desired glucose level was reduced by half in the obese patients compared with that of normal subjects. Thus, in healthy as well as obese hyperinsulinemic subjects, insulin at concns. capable of suppressing its basal secretion fails to suppress its glucose-stimulated secretion.

Structural stability in the 4-zinc human insulin hexamer

Structural stability in the 4-zinc human insulin hexamer. Smith, G. D.; Swenson, D. C.; Dodson, E. J.; Dodson, G. G.; Reynolds, C. D. (Med. Found. Buffalo Inc., Buffalo, NY 14203, USA). Proc. Natl. Acad. Sci. U. S. A., 81(22), 7093-7 (English) 1984. CODEN: PNASA6. ISSN: 0027-8424. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The present study reports the crystal structure of 4-zinc human insulin [11061-68-0], which is used clin. as a slow-acting prepn. The structure has been refined, using 1.85-? resoln. data, to a residual of 0.173. The unit cell is rhombohedral, space group R3, with hexagonal cell consts. a = 80.953 and c = 37.636 ?, and it is nearly isomorphous with that of 4-Zn porcine insulin. As a result of a conformational change of the 1st 8 residues of the B-chain of mol. 1 from an extended conformation obsd. in the 2-Zn structure to an a-helical one, the coordination around one of the Zn ions on the 3-fold axis has changed, an addnl. Zn ion in a general position is bound by the hexamer, and addnl. H-bonded interactions help stabilize dimer and hexamer formation. Unlike the surface of the 2-Zn insulin hexamer, which possesses a shallow depression contg. a Zn ion and its coordinating water mols., the 4-Zn human insulin hexamer contains a Zn and chloride ion at the bottom of an 8-? tunnel produced by 3 parallel a-helices. These a-helices shield the Zn ion from the environment, decreasing the rate of dissocn. of the hexamer, and provide an explanation for the slow-acting aspect of the 4-Zn cryst. form.