Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently found that in nondiabetic dogs and humans, suppression of glucose production (GP) is mediated by both peripheral and hepatic effects of insulin. We have also found that both nonesterified fatty acids (NEFA) and glucagon are important determinants of the peripheral effect of insulin on GP. However, in moderately hyperglycemic depancreatized dogs, suppression of GP appeared to be mediated by peripheral but not hepatic insulin. In this latter study, insulin concentrations were in the high postprandial range (approximately 300 pmol/L) and suppression of GP may have been close to maximum. The aim of the present study was to determine whether GP can be regulated by hepatic insulin in depancreatized dogs at low insulin concentrations in the postabsorptive range. Depancreatized dogs were maintained at moderately hyperglycemic levels (approximately 10 mmol/L) by subbasal insulin infusions. In paired experiments, additional low-dose equimolar insulin infusions (0.75 pmol/kg x min) were administered peripherally (PER, n = 6) or portally (POR, n = 6) during glucose clamps. This resulted in a minimal increase in peripheral insulin levels, which was greater in PER versus POR, 29.0 +/- 3.7 versus 11.7 +/- 2.2 pmol/L. Also, we infused insulin peripherally at half this rate (1/2 PER, n = 6) to match the increase in peripheral insulin levels in POR (1/2 PER, 14.6 +/- 2.2) and thus obtain a selective POR versus 1/2 PER difference in hepatic sinusoidal insulin levels. PER suppressed GP more than POR (45.4% +/- 4.0% v 35.3% +/- 6.8%, P < .001), whereas POR did not suppress GP more than 1/2 PER (35.6% +/- 6.3%). Therefore, suppression of GP was proportional to peripheral rather than hepatic sinusoidal insulin levels, as in our previous study at higher insulin concentrations. In conclusion, during glucose clamps in moderately hyperglycemic depancreatized dogs, (1) suppression of GP was dominated by insulin's peripheral effects not only at postprandial but also postabsorptive insulin levels, and (2) we found no evidence for a hepatic effect of insulin in suppressing GP. We hypothesize that this effect is reduced in the depancreatized dog model of diabetes due to hepatic insulin resistance and/or hyperglycemia.
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PMID:Increased dependence of glucose production on peripheral insulin in diabetic depancreatized dogs. 1002 74

The aim of the present study was to determine whether a decrease in the portal vein insulin level during non-insulin-induced hypoglycemia is sensed and is responsible for the normal increase in glucagon release from the alpha cell. To address this aim, a glycogen phosphorylase inhibitor was used to create mild, non-insulin-induced hypoglycemia in 2 groups of 18-hour fasted conscious dogs. Arterial insulin was clamped at a basal level in both groups, but in one group (PE) the portal vein insulin level was permitted to fall by approximately 65% while in the other group (POR) it was clamped at a basal level. In both groups glucose was infused at a variable rate to clamp the plasma glucose level at approximately 70 mg/dL. Plasma glucagon (pg/mL) rose to indistinguishable maxima in both groups (56 +/- 3 in PE and 67 +/- 9 in POR). Likewise, glucagon secretion (pg/kg/min) increased similarly (189 +/- 32 to 455 +/- 203 in PE and 192 +/- 50 to 686 +/- 237 in POR). Thus, the increase in glucagon release was not inhibited when the portal vein insulin level was prevented from decreasing (POR group). Clearly, a fall in the portal vein insulin level is not required for a normal alpha-cell response to mild, non-insulin-induced hypoglycemia.
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PMID:A fall in portal vein insulin does not cause the alpha-cell response to mild, non-insulin-induced hypoglycemia in conscious dogs. 1462

After a meal, glucagon-like peptide-1 (GLP-1) levels in the hepatic portal vein are elevated and are twice those in peripheral blood. The aim of this study was to determine whether any of GLP-1's acute metabolic effects are initiated within the hepatic portal vein. Experiments consisted of a 40-min basal period, followed by a 240-min experimental period, during which conscious 42-h-fasted dogs received glucose intraportally (4 mgxkg(-1)xmin(-1)) and peripherally (as needed) to maintain arterial plasma glucose levels at approximately 160 mg/dl. In addition, saline was given intraportally (CON; n = 8) or GLP-1 (1 pmolxkg(-1)xmin(-1)) was given into the hepatic portal vein (POR; n = 11) or the hepatic artery (HAT; n = 8). Portal vein plasma GLP-1 levels were basal in CON, 20x basal in POR, and 10x basal in HAT, whereas levels in the periphery and liver were the same in HAT and CON. The glucose infusion rate required to maintain hyperglycemia was significantly greater in POR (8.5 +/- 0.7 mgxkg(-1)xmin(-1), final 2 h) than in either CON or HAT (6.0 +/- 0.5 or 6.7 +/- 1.0 mgxkg(-1)xmin(-1), respectively). There were no differences among groups in either arterial plasma insulin (24 +/- 2, 23 +/- 3, and 23 +/- 3 microU/ml for CON, POR, and HAT, respectively) or glucagon (23 +/- 2, 30 +/- 3, and 25 +/- 2 pg/ml) levels during the experimental period. The increased need for glucose infusion reflected greater nonhepatic as opposed to liver glucose uptake. GLP-1 infusion increased glucose disposal independently of changes in pancreatic hormone secretion but only when the peptide was delivered intraportally.
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PMID:Intraportal GLP-1 infusion increases nonhepatic glucose utilization without changing pancreatic hormone levels. 1768 4