Search

Glucose-dependent insulinotropic polypeptide or gastric inhibitory polypeptide (GIP) is a 42 amino acid intestinal hormone, which exhibits several direct and indirect effects on fat and glucose metabolism. To determine the bioactive region(s) of the molecule, synthetic and proteolytic fragments of the hormone were generated and tested for their ability to induce a biological response in the isolated, perfused rat pancreas and stomach. A synthetic fragment corresponding to porcine GIP residues 1-30 retained strong insulinotropic activity in the isolated, perfused rat pancreas but greatly reduced somatostatinotropic activity in the isolated perfused rat stomach. A synthetic fragment corresponding to porcine GIP residues 15 to 30 was biologically inactive. However, enterokinase treatment of the synthetic 15-30 fragment restored partial insulinotropic activity in the isolated, perfused rat pancreas. The hypothesis that the restoration of biological activity was due to the enzymatic removal of the amino-terminal dipeptide (Asp-Lys) of GIP15-30 was supported by the observation that a synthetic fragment lacking these two residues was also insulinotropic. Further fractionation of the molecule generated a biologically active 19-30 fragment, suggesting that the residues necessary for the insulin response are contained within this region.

Glucose-dependent insulinotropic polypeptide (GIP) is a forty-two amino acid hormone that stimulates the secretion of insulin from the pancreatic B-cells in the presence of elevated glucose concentrations. The human GIP gene with the human A alpha-fibrinopeptide sequence was synthesized and linked to the Staphylococcus aureus protein A gene in the vector pRIT2T. This plasmid was expressed in Escherichia coli, and the resulting fusion protein consisted of three domains: protein A for ease of purification, fibrinopeptide sequence for thrombin cleavage and human GIP. The GIP was subsequently cleaved from the fusion protein with alpha-thrombin. The identity of the recombinant human GIP was confirmed by SDS-PAGE, ELISA, HPLC and amino-terminal amino acid sequence analysis. This recombinant product was shown to have comparable insulinotropic activity to porcine GIP in the isolated perfused pancreas.

Despite efforts to develop methods for measuring the quality of medical care, no satisfactory mechanism has been established. Our study, using hypertension as a clinical model, evaluated process and outcomes separately and then compared the two. Physician adherence to an extensive process list varied substantially from established criteria. No statistically significant association was detected between process and outcome. Regression analysis examined the relation between outcome diastolic pressure and 12 predictive variables that included patient satisfaction and social class. The only statistically significant variables (P less than 0.05) related to outcome blood pressure were age, initial blood pressure and weight. The inability to identify a relation between various process items and outcome suggests that, in determining a successful outcome for hypertensive patients, the selective use of process by the physician may be more effective than adherence to a rigid criteria list.