Osei K, Falko J M, O'Dorisio T M, Fields P G, Bossetti B
J Clin Endocrinol Metab. 1986 Feb;62(2):325-30. doi: 10.1210/jcem-62-2-325.
Gastric inhibitory polypeptide (GIP) has insulinotropic actions in the presence of hyperglycemia. However, its extrapancreatic effects on glucose homeostasis are controversial. We have studied the relationships between GIP and immunoreactive insulin (IRI) and glucose turnover rates (D3H-3 glucose technique) in five poorly controlled type II diabetic patients and five normal subjects before and after a breakfast containing 500 kcal including 42 g sucrose. Mean fasting serum glucose levels and glucose responses were significantly (P less than 0.001) higher in the diabetic patients than in normal subjects. Mean basal serum IRI levels were similar in both groups [12.8 +/- 2.9 (SEM) vs. 11.8 +/- 2 microU/ml, P = NS]. After meal ingestion, mean IRI levels rose significantly to a peak at 20 min in the normal subjects but the responses were blunted in the diabetic patients (74 +/- 10 vs. 24 +/- 6 microU/ml, P less than 0.001). At all other times studied (60-180 min), mean serum IRI levels were similar in the diabetic patients and the normal subjects except at 180 min. Mean basal serum GIP levels were similar in the diabetic patients and the normal subjects (538 +/- 100 vs. 400 +/- 50 pg/ml, P = NS). After meal ingestion, mean GIP levels rose between 0-60 min but were significantly higher in the diabetic patients only at 20 min (1200 +/- 190 vs. 566 +/- 76 pg/ml, P less than 0.01). Mean basal hepatic glucose output was higher (P less than 0.01) in the diabetic patients. However, the mean basal MCR values were similar. After meal ingestion, total splanchnic glucose output and rates of glucose utilization (RU) were significantly higher in the diabetic patients compared with the normal subjects (P less than 0.001, and P less than 0.001, respectively). Postmeal MCR values were not statistically different in both groups. There were significant positive correlations between postmeal splanchnic glucose output and both IRI (r = 0.805, P less than 0.005) and GIP (r = 0.749, P less than 0.02) in the diabetic patients but not in the normal subjects (r = 0.10, P = NS for both). Whereas no relationships existed between RU and IRI in either group, RU correlated strongly with GIP (r = 0.810, P less than 0.005) only in the diabetic patients. We hypothesize that GIP may play a compensatory role to improve both impaired beta-cell insulin release and peripheral glucose utilization which are the recognized pathogenetic mechanisms underlying type II diabetes mellitus.
胃抑制性多肽（GIP）在血糖升高时具有促胰岛素分泌作用。然而，其对葡萄糖稳态的胰腺外作用存在争议。我们研究了5例血糖控制不佳的II型糖尿病患者和5例正常受试者在摄入含500千卡热量（包括42克蔗糖）的早餐前后，GIP与免疫反应性胰岛素（IRI）及葡萄糖周转率（D3H - 3葡萄糖技术）之间的关系。糖尿病患者的空腹血清葡萄糖平均水平和葡萄糖反应显著高于正常受试者（P < 0.001）。两组的基础血清IRI平均水平相似[12.8 ± 2.9（SEM）对11.8 ± 2微单位/毫升，P = 无显著性差异]。进食后，正常受试者的IRI平均水平在20分钟时显著升高至峰值，但糖尿病患者的反应减弱（74 ± 10对24 ± 6微单位/毫升，P < 0.001）。在其他所有研究时间点（60 - 180分钟），糖尿病患者和正常受试者的血清IRI平均水平相似，但180分钟时除外。糖尿病患者和正常受试者的基础血清GIP平均水平相似（538 ± 100对400 ± 50皮克/毫升，P = 无显著性差异）。进食后，GIP平均水平在0 - 60分钟之间升高，但仅在20分钟时糖尿病患者显著高于正常受试者（1200 ± 190对566 ± 76皮克/毫升，P < 0.01）。糖尿病患者的基础肝脏葡萄糖输出较高（P < 0.01）。然而，基础MCR值相似。进食后，糖尿病患者的总内脏葡萄糖输出和葡萄糖利用率（RU）显著高于正常受试者（分别为P < 0.001和P < 0.001）。两组餐后MCR值无统计学差异。糖尿病患者餐后内脏葡萄糖输出与IRI（r = 0.805，P < 0.005）和GIP（r = 0.749，P < 0.02）均呈显著正相关，但正常受试者无此相关性（两者r = 0.10，P = 无显著性差异）。两组中RU与IRI均无相关性，仅糖尿病患者中RU与GIP密切相关（r = 0.810，P < 0.005）。我们推测，GIP可能发挥代偿作用，改善受损的β细胞胰岛素释放和外周葡萄糖利用，而这是公认的II型糖尿病发病机制。
