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The effect of Biosynthetic Human Proinsulin on glucose uptake by skeletal muscle was studied in the isolated perfused hindquarter of fasted rats. Animals were randomly assigned to the control group, insulin-perfused or proinsulin-perfused group. Glucose disappearance from the perfusate and muscle glycogen levels before and after 2 hours perfusion were measured. Perfusate glucose concentration showed the greatest decline in the insulin group, which was significantly lower (p < .01) than control from 60 to 120 min. Proinsulin perfusion resulted in a smaller and delayed decrease in perfusate glucose. The proinsulin perfusate glucose levels were significantly higher (p < .05) than the insulin glucose values during the second hour of perfusion. After the first hour of perfusion, insulin infusion resulted in higher rates of glucose uptake than control (p < .005) or proinsulin infusion (p < .05). The glucose uptake by muscles perfused with proinsulin was significantly different from control values only at the 2 hour time point (p < .05). Glycogen concentration following insulin infusion increased significantly in the oxidative muscles, i.e. soleus (p < .05) and red vastus (p < .002). These increases in glycogen were significantly different from the changes observed in muscles of control animals. The plantaris and white vastus muscles, which have fast twitch fibers, did not show a significant response to insulin. Proinsulin perfusion decreased glycogen levels regardless of the muscle type. This decline was significantly different from the glycogen changes in soleus (p < .025), plantaris (p < .001) and white vastus (p < .05) muscles of control animals. The proinsulin glycogen fall was also significantly different from the insulin induced response in soleus, plantaris and red vastus muscles (p < .001). These results show that proinsulin has 8.6 % of the biologic potency of insulin for glucose uptake in rat skeletal muscle. Insulin induced an increase in glycogen concentration in oxidative muscles, but proinsulin elicted a drop in glycogen level regardless of the muscle type.

Background: Attaining optimal glucose control in type 2 diabetes (T2DM) is essential to minimise complications, but difficult to achieve in practice with declining β-cell function in patients. Aim: To evaluate the efficacy and feasibility of a protocol-led, treat-to-target approach emphasising earlier oral hypoglycaemic agent (OHA) combination and insulin use to target basal and prandial glucose in primary care. Methods: T2DM patients aged 40-75 years, with glycosylated haemoglobin (HbA_1C) 6.4-10.0% on diet or oral monotherapy in 7 practices were asked to participate in a protocol-led, target-driven programme of care using early OHA and insulin therapy combinations to target basal and prandial glucose. Recruited patients were randomised to pre-specified algorithms with monthly therapy adjustment aiming for fasting plasma glucose values (FPG) <6mmol/L and 2-hour post-prandial (PPG) <8mmol/L. Isophane or humalog insulin was added where glucose targets were not attained. All patients were reviewed at one year. Glucose, weight and cardiovascular (CVS) risk factor outcomes were measured and the feasibility, acceptability and safety of the programme evaluated with validated questionnaires. Results: 345 patients were studied. 60 participated in the glucose study and 285 received standard care. 65% of recruited patients were male, with mean (SD) age 61.0 (8.2) years, BMI 29.8 (5.3) kg/m2, HbA_1C 7.5 (0.9)% and median (IQR) T2DM duration 3 (1-5) years. 41 completed the study. Glucose control was significantly improved in recruited compared to non-recruited patients with a mean overall 0.8% HbA_1C reduction and 72% patients achieving HbA_1C<7% and 64% <6.5% at 1 year. Therapy use was also significantly increased with 50% requiring 3 therapies, 30% 2 and 10% monotherapy. 24 (59%) of recruited patients received isophane and 16 (39%) humalog to achieve targets. Glucose optimisation was achieved without significant hypoglycaemia or adverse events and patient quality of life (QoL) and therapy satisfaction remained high. CVS risk was reduced in recruited patients. Conclusions: A more structured, target-driven approach to glucose optimisation can successfully achieve normoglycaemia in a selected primary care T2DM population without significant adverse events, hypoglycaemia. or QoL impairment in patients. A principal barrier to wider implementation of this programme appears to be practice and patient participation.

Thesis (M.S.)--University of Hawaii at Manoa, 2005. / Includes bibliographical references (leaves 88-90). / xii, 90 leaves, bound ill. (some col.) 29 cm

Thesis (M.S.)--Auburn University, 2007. / Abstract. Vita. Includes bibliographic references (ℓ. 46-53)

Thesis--Auburn University, 2009. / Abstract. Vita. Includes bibliographical references (p. 27-33).

Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 171-177). Available also in a digital version from Dissertation Abstracts.

The measurement of glycated proteins, in particular, glycated albumin using specific antibodies offers the much-needed possibility of a (semi) automated method for the diagnosis and monitoring of diabetic control. Glycated proteins would appear to be poor immunogens as is evident by the lack of antibodies successfully raised against them when compared against the number of antibodies recognising reduced-glycated proteins. This study has successfully overcome this problem by synthesing several different glycated compounds as haptens and then using them in conjunction with a carrier protein to raise antisera in sheep. The binding of one of these antisera, with a titre 1:100000 showed considerable displacement when incubated with diabetic plasma at various dilutions. Western blot analysis on human plasma confirmed that the antiserum specifically recognised a continuous epitope on glycated human serum albumin. Affinity purified antibodies were used to develop both an indirect competitive ELISA and later a direct non-competitive ELISA for glycated serum albumin which does not require prior reduction of the glycated protein to the glucitol form. These assays have a dynamic range at 0 to 100 mug/ml and 0 to 50mug/ml of glycated human serum albumin respectively. The competitive ELISA exhibited < 0.15% cross reactivity with both sodium borohydride and sodium periodate treated human serum albumin. Further work was needed to be undertaken to develop a rugged ELISA that could discriminate between diabetics and normals by routinely measuring glycated human serum albumin levels.